Behavior Of Breast Cancer Cells Research Articles

Oleic acid inhibits the migration and invasion of breast cancer cells with stemness characteristics through oxidative stress-mediated attenuation of the FAK/AKT/NF-κB pathway

Oleic acid, found in a variety of food sources, is beneficial to health. However, studies on its anticancer effects on cancer stem cells resistant to conventional treatments and on the mechanisms underlying such effects are scarce. Here, we evaluated the anticancer effects of oleic acid against breast cancer cells with stemness characteristics. Oleic acid inhibited the proliferation of breast cancer stem-like cells more significantly than that of their respective parental cells, and reduced the expression of stem cell markers and migration and invasion propensity. It also repressed the phosphorylation of FAK, AKT, and NF-κB, proteins involved in cell migration and invasion. Oleic acid-induced increase in reactive oxygen species levels mediated the inhibition of the FAK/AKT/NF-κB signaling axis. Our study demonstrates that oleic acid-induced oxidative stress plays an important role in inhibiting the metastatic behavior of breast cancer cells with stemness characteristics and is relevant for management of treatment-resistant breast cancer.

Cryoprotective isoliquiritigenin-zein phosphatidylcholine nanoparticles inhibits breast cancer-bone metastasis by targeting JAK-STAT signaling pathways

Breast cancer (BC) is the most common cancer in women and is known for its tendency to spread to the bones, causing significant health issues and mortality. In this study, we aimed to investigate whether cryoprotective isoliquiritigenin-zein phosphatidylcholine nanoparticles (ISL@ZLH NPs) could inhibit BC-induced bone destruction and tumor metastasis in both in vitro and animal models. To evaluate the potential of ISL@ZLH NPs, we conducted various experiments. First, we assessed cell viability, colony formation, transwell migration, and wound healing assays to determine the impact of ISL@ZLH NPs on BC cell behavior. Western blotting, TRAP staining and ALP activity were performed to examine the effects of ISL@ZLH NPs on osteoclast formation induced by MDA-MB-231 cell-conditioned medium and RANKL treated RAW 264.7 cells. Furthermore, we assessed the therapeutic impact of ISL@ZLH NPs on tumor-induced bone destruction using a mouse model of BC bone metastasis. Treatment with ISL@ZLH NPs effectively suppressed BC cell proliferation, colony formation, and motility, reducing their ability to metastasize. ISL@ZLH NPs significantly inhibited osteoclast formation and the expression of factors associated with bone destruction in BC cells. Additionally, ISL@ZLH NPs suppressed JAK-STAT signaling in RAW264.7 cells. In the BCBM mouse model, ISL@ZLH NPs led to a significant reduction in osteolytic bone lesions compared to the control group. Histological analysis and TRAP staining confirmed that ISL@ZLH NPs preserved the integrity of bone structure, preventing invasive metastasis by confining tumor growth to the bone marrow cavity. Furthermore, ISL@ZLH NPs effectively suppressed tumor-induced osteoclastogenesis, a key process in BC-related bone destruction. Our findings demonstrate that ISL@ZLH NPs have the potential to inhibit BC-induced bone destruction and tumor metastasis by targeting JAK-STAT signaling pathways and suppressing tumor-induced osteoclastogenesis. These results underscore the therapeutic promise of ISL@ZLH NPs in managing BC metastasis to the bones.

A Theoretical Approach to Study the Frequency Dependent Dielectric behavior of Breast Cancer Cells using AlN buffer-based AlGaN/GaN HEMT

Abstract This article investigates the applicability of open gated high electron mobility transistor (HEMT) as a biosensing platform for Breast cancer detection. The present study reports the detection of healthy (MDA-10) and malignant cells (MDA-MB-231) associated with breast cancer using high-quality AlN buffer AlGaN/GaN HEMT with dual cavity structure formed by etching out the gate metal from source and drain sides under the gate region. The AlN buffer AlGaN/GaN HEMT provides better 2DEG confinement and large conduction band offset than GaN buffer. The proposed design is analyzed at frequencies of 900 MHz and 10 GHz, as breast cells have distinct dielectric properties at different microwave frequencies. The variation in dielectric constant of the cavity region corresponding to biomolecular species will change the device’s electrical characteristics and hence can be used to detect breast cancer cells. In this work, the device sensing parameters considered for analysis are shift in threshold voltage and drain current sensitivity. The device performance has also been analyzed by optimizing cavity thickness and length to select the best design for the sensing. The effect of non-ideal conditions such as steric hindrance and probing is also studied by emulating these real time effects in simulation. The device shows a maximum drain current sensitivity of 29.94% for 20 nm of cavity thickness and 1µm of the cavity length. The results depict that the proposed device design exhibits a highly sensitive response and can be promising alternate for future biosensing applications.

Lung-derived soluble factors support stemness/plasticity and metastatic behaviour of breast cancer cells via the FGF2-DACH1 axis.

Patients with triple-negative breast cancer (TNBC) have an increased propensity to develop lung metastasis. Our previous studies demonstrated that stem-like ALDHhiCD44+ breast cancer cells interact with lung-derived soluble factors, resulting in enhanced migration and lung metastasis particularly in TNBC models. We have also observed that the presence of a primary TNBC tumor can 'prime' the lung microenvironment in preparation for metastasis. In this study, we hypothesized that soluble lung-derived factors secreted in the presence of a primary TNBC tumor can influence stemness/plasticity of breast cancer cells. Using an ex vivo pulmonary metastasis assay (PuMA), we observed that the lung microenvironment supports colonization and growth of ALDHhiCD44+ TNBC cells, potentially via interactions with lung-derived FGF2. Exposure of TNBC cells to lung-conditioned media (LCM) generated from mice bearing TNBC primary tumors (tbLCM) significantly enhanced the proportion of ALDHhiCD44+ cells compared to control or LCM from tumor-naïve mice (tnLCM). Further analysis using a human cancer stem cell qPCR array revealed that, relative to tnLCM or control, exposure of TNBC cells to tbLCM leads to downregulation of the transcription factor and putative tumor suppressor Dachshund homolog 1 (DACH1), a downstream regulator of FGF2. In addition, inhibition of DACH1 using siRNA or treatment with recombinant FGF2 enhanced the ALDHhiCD44+ phenotype. Taken together, our findings suggest that the FGF2-DACH1 signaling axis supports stemness/plasticity of TNBC cells in the lung microenvironment and lays the foundation for future evaluation of FGF2 as a potential novel therapeutic target for treatment or prevention of breast cancer metastasis to the lung.

Abstract LB009: Unveiling the significance of DARPP-32 and its partners, including GRB7 and DKK1, in breast cancer: Integrative insights from patient data and cell line transcriptomics

Abstract DARPP-32 plays a crucial role in regulating both protein-phosphatase-1 (PP-1) and protein kinase A (PKA), its function being reliant on its phosphorylation status. We have previously demonstrated that low DARPP-32 expression is associated with adverse survival of breast cancer patients, particularly those with oestrogen receptor (ER) positive disease; however, there is limited information on how DARPP-32 may alter breast cancer cell behaviour. We have recently published an integrative approach using patient data and cell line transcriptomics to understand the role of DARPP-32 in breast cancer. We analysed the transcriptome of T47D ER positive breast cancer cells following DARPP-32 knockdown, including treatments in combination with 17β-estradiol or PKA inhibitor fragment (6-22) amide. 202 differentially expressed transcripts were identified in DARPP-32 knock down cells and treatment of these cells with 17β-estradiol or PKA inhibitor fragment (6-22) amide led to the differential expression of 193 and 181 transcripts respectively. Differentially expressed transcripts were compared with genes identified as associated with DARPP-32 expression in 1980 breast cancer patients within the METABRIC cohort using an Artificial Neural Network approach (ANN). Several genes overlapped with those identified from cell line transcriptomics, including PTK7, TRAF5, and KLK6. Both DKK1 and GRB7 were identified as genes associated with DARPP-32 expression in patients using ANN, therefore protein expression was determined in a large cohort of early-stage breast cancer patients (n>1000). We demonstrated that DKK1 and GRB7 protein expression was significantly correlated with DARPP-32 Threonine-34 phosphorylation levels within the same samples (all P<0.05). We have now applied an ANN-based integrative data mining approach to identify genes with the largest effect on other genes resulting in an interactome map, which was based on genes identified within the cell line transcriptomics and original ANN. 1878 genes were identified for inclusion within an interactome map in the total patient cohort, whereas 1003 were identified in ER negative disease alone and 2144 in ER positive disease alone. Pathway enrichment analysis identified the ubiquitin proteosome pathway, the insulin pathway-protein kinase B signalling cascade and the RAS pathway. This study underscores the significance of DARPP-32, a central molecular switch, in breast cancer, elucidating its impact on patient prognosis and highlighting potential molecular targets for therapeutic intervention. The integrative approach combining patient data with cell line transcriptomics provides insights into the complex mechanisms underlying breast cancer progression and opens avenues for further research and targeted interventions. Citation Format: Behnaz Saidy, Richa Vasan, Megan-Rose Greener, Rosie Durrant, Adelynn Immanuel, Andrew Green, Emad Rakha, Ian Ellis, Graham Ball, Stewart Martin, Sarah J. Storr. Unveiling the significance of DARPP-32 and its partners, including GRB7 and DKK1, in breast cancer: Integrative insights from patient data and cell line transcriptomics [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr LB009.

Mammary tissue-derived extracellular matrix hydrogels reveal the role of irradiation in driving a pro-tumor and immunosuppressive microenvironment

Radiation therapy (RT) is essential for triple negative breast cancer (TNBC) treatment. However, patients with TNBC continue to experience recurrence after RT. The role of the extracellular matrix (ECM) of irradiated breast tissue in tumor recurrence is still unknown. In this study, we evaluated the structure, molecular composition, and mechanical properties of irradiated murine mammary fat pads (MFPs) and developed ECM hydrogels from decellularized tissues (dECM) to assess the effects of RT-induced ECM changes on breast cancer cell behavior. Irradiated MFPs were characterized by increased ECM deposition and fiber density compared to unirradiated controls, which may provide a platform for cell invasion and proliferation. ECM component changes in collagens I, IV, and VI, and fibronectin were observed following irradiation in both MFPs and dECM hydrogels. Encapsulated TNBC cell proliferation and invasive capacity was enhanced in irradiated dECM hydrogels. In addition, TNBC cells co-cultured with macrophages in irradiated dECM hydrogels induced M2 macrophage polarization and exhibited further increases in proliferation. Our study establishes that the ECM in radiation-damaged sites promotes TNBC invasion and proliferation as well as an immunosuppressive microenvironment. This work represents an important step toward elucidating how changes in the ECM after RT contribute to breast cancer recurrence.

Exploring the Evolving Significance of lncRNA TUG1-mediated Signaling Pathways in Breast Cancer

Abstract: Breast cancer is one of the most common malignancies in women worldwide. Invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC) are the most common kinds of invasive breast cancer. Several genetic, epigenetic, and environmental factors could trigger the pathogenesis of breast cancer. Breast cancer treatment generally includes surgery, radiation therapy, chemotherapy, hormonal treatment, targeted therapy, immunotherapeutic, neoadjuvant systemic therapy, and systemic therapy. Although several classical treatment methods are used in cancer therapy, molecular-based strategies can open a new perspective for breast cancer treatment. Previous studies reported that long non-coding RNAs (lncRNAs) play important roles in cancer development and progression. LncRNA TUG1 was found to target several miRNAs and regulate breast cancer cell behavior. TUG1 can induce cell proliferation and invasion of breast cancer cells via downregulation of some miRNAs. Therefore, TUG1 might be a potent biomarker for the treatment of human cancer. In this review, we summarized the functional roles of TUG1 in breast cancer.

Single-cell and whole-transcriptome sequencing of lymph node metastasis-related gene signature: A large-scale pan-cancer cohort, machine learning and experimental study.

Lymph node metastasis (LNM) is an independent prognostic factor in numerous types of cancer. Therefore, a LNM-related gene-based nomogram may precisely predict survival and drug sensitivity, and reveal the mechanism underlying LNM. Gene sequencing profiles of pan-cancer data (33 cancer types) were acquired from The Cancer Genome Atlas UCSC Xena database. Patients were classified into primary (N = 10,071) and testing (N = 5,036) cohorts. The lymph node score (LNscore) was established via single-cell RNA sequencing, whole-transcriptome sequencing, machine learning, and Cox regression analyses. A novel prognosis model, formulated by incorporating the LNscore and clinical characteristics, was evaluated using the concordance index, calibration curve, and decision curve analysis. Moreover, patients were assigned into high- and low-risk groups according to the median LNscore. We investigated these two groups for survival prognosis, functional enrichment, immune infiltration, and drug sensitivity. In addition, we silenced and overexpressed insulin like growth factor 2 mRNA binding protein 2 (IGF2BP2). We also analyzed the behavior of breast cancer (BRCA) cells regarding lymphatic metastasis and lymphangiogenesis in vitro. IGF2BP2 stimulated the proliferation of BRCA cells via 5-Ethynyl-2'-deoxyuridine and Cell Counting Kit-8 experiments. A LNM-related set of 12 genes was identified and utilized to determine the LNscore. The concordance-index of both cohorts in the LNscore-based model was >0.7. The immune landscape revealed that the sensitivity to immunotherapy might be better in the high-risk group versus the low-risk group. In addition, we discovered that IGF2BP2 was overexpressed in BRCA tissues and significantly associated with poor survival. Functional analysis indicated that IGF2BP2 promoted BRCA cell migration and proliferation. Additionally, IGF2BP2 accelerated lymphatic metastasis and lymphangiogenesis in vivo. A novel LNscore-based model was established via comprehensive analysis of LNM-related genes. This model can accurately predict patient survival and drug sensitivity, and reveal the mechanism of LNM in the pan-cancer setting.

Ultrasound Microbubble-Stimulated miR-145-5p Inhibits Malignant Behaviors of Breast Cancer Cells by Targeting ACTG1.

Ultrasound-targeted microbubble destruction (UTMD) technology combines ultrasound with a variety of functional microbubble vectors to enhance the transfection and expression of target genes, and has become a promising noninvasive method for localized gene transfer, which is widely used in gene therapy for cancer. This research aimed to explore the role of UTMD-mediated miR-145-5p on breast cancer (BC) tumorigenesis and the underlying mechanisms. To achieve UTMD-mediated miR-145-5p overexpression, BC cells were cotransfected with microbubbles (MBs) and miR-145-5p mimics. The BC cell malignant phenotypes were assessed through CCK-8, wound healing, and transwell assays. MiR-145-5p and actin gamma 1 (ACTG1) binding relationship was verified through luciferase reporter and RNA pull-down assays. MiR-145-5p and ACTG1 levels in BC cells and tissues were detected through RT-qPCR and Western blotting. ACTG1 was upregulated, whereas miR-145-5p was downregulated in BC cells and tissues. MiR-145-5p targeted ACTG1 and negatively regulated its level in BC cells. Overexpressing miR-145-5p restrained BC cell growth, migration, and invasion. Ultrasound-targeted microbubble destruction improved the overexpression efficiency of miR-145-5p and enhanced the suppressive influence on BC cell malignant phenotypes. In addition, ACTG1 overexpression compromises the repression of UTMD-mediated miR-145-5p on cellular behaviors in BC. Ultrasound-targeted microbubble destruction-delivered miR-145-5p hindered malignant behaviors of BC cells through downregulating ACTG1.

Experimental measurement and numerical modeling of deformation behavior of breast cancer cells passing through constricted microfluidic channels

During the multistep process of metastasis, cancer cells encounter various mechanical forces which make them deform drastically. Developing accurate in-silico models, capable of simulating the interactions between the mechanical forces and highly deformable cancer cells, can pave the way for the development of novel diagnostic and predictive methods for metastatic progression. Spring-network models of cancer cell, empowered by our recently proposed identification approach, promises a versatile numerical tool for developing experimentally validated models that can simulate complex interactions at cellular scale. Using this numerical tool, we presented spring-network models of breast cancer cells that can accurately replicate the experimental data of deformation behavior of the cells flowing in a fluidic domain and passing narrow constrictions comparable to microcapillary. First, using high-speed imaging, we experimentally studied the deformability of breast cancer cell lines with varying metastatic potential (MCF-7 (less invasive), SKBR-3 (medium-high invasive), and MDA-MB-231 (highly invasive)) in terms of their entry time to a constricted microfluidic channel. We observed that MDA-MB-231, that has the highest metastatic potential, is the most deformable cell among the three. Then, by focusing on this cell line, experimental measurements were expanded to two more constricted microchannel dimensions. The experimental deformability data in three constricted microchannel sizes for various cell sizes, enabled accurate identification of the unknown parameters of the spring-network model of the breast cancer cell line (MDA-MB-231). Our results show that the identified parameters depend on the cell size, suggesting the need for a systematic procedure for identifying the size-dependent parameters of spring-network models of cells. As the numerical results show, the presented cell models can simulate the entry process of the cell into constricted channels with very good agreements with the measured experimental data.

The importance of cancer-associated fibroblasts in targeted therapies and drug resistance in breast cancer.

Cancer-associated fibroblasts (CAFs) play a substantial role in the tumor microenvironment, exhibiting a strong association with the advancement of various types of cancer, including breast, pancreatic, and prostate cancer. CAFs represent the most abundant mesenchymal cell population in breast cancer. Through diverse mechanisms, including the release of cytokines and exosomes, CAFs contribute to the progression of breast cancer by influencing tumor energy metabolism, promoting angiogenesis, impairing immune cell function, and remodeling the extracellular matrix. Moreover, CAFs considerably impact the response to treatment in breast cancer. Consequently, the development of interventions targeting CAFs has emerged as a promising therapeutic approach in the management of breast cancer. This article provides an analysis of the role of CAFs in breast cancer, specifically in relation to diagnosis, treatment, drug resistance, and prognosis. The paper succinctly outlines the diverse mechanisms through which CAFs contribute to the malignant behavior of breast cancer cells, including proliferation, invasion, metastasis, and drug resistance. Furthermore, the article emphasizes the potential of CAFs as valuable tools for early diagnosis, targeted therapy, treatment resistance, and prognosis assessment in breast cancer, thereby offering novel approaches for targeted therapy and overcoming treatment resistance in this disease.

PRRG4 regulates mitochondrial function and promotes migratory behaviors of breast cancer cells through the Src-STAT3-POLG axis

BackgroundBreast cancer is the leading cause of cancer death for women worldwide. Most of the breast cancer death are due to disease recurrence and metastasis. Increasingly accumulating evidence indicates that mitochondria play key roles in cancer progression and metastasis. Our recent study revealed that transmembrane protein PRRG4 promotes the metastasis of breast cancer. However, it is not clear whether PRRG4 can affect the migration and invasion of breast cancer cells through regulating mitochondria function.MethodsRNA-seq analyses were performed on breast cancer cells expressing control and PRRG4 shRNAs. Quantitative PCR analysis and measurements of mitochondrial ATP content and oxygen consumption were carried out to explore the roles of PRRG4 in regulating mitochondrial function. Luciferase reporter plasmids containing different lengths of promoter fragments were constructed. Luciferase activities in breast cancer cells transiently transfected with these reporter plasmids were analyzed to examine the effects of PRRG4 overexpression on promoter activity. Transwell assays were performed to determine the effects of PRRG4-regulated pathway on migratory behaviors of breast cancer cells.ResultsAnalysis of the RNA-seq data revealed that PRRG4 knockdown decreased the transcript levels of all the mitochondrial protein-encoding genes. Subsequently, studies with PRRG4 knockdown and overexpression showed that PRRG4 expression increased mitochondrial DNA (mtDNA) content. Mechanistically, PRRG4 via Src activated STAT3 in breast cancer cells. Activated STAT3 in turn promoted the transcription of mtDNA polymerase POLG through a STAT3 DNA binding site present in the POLG promoter region, and increased mtDNA content as well as mitochondrial ATP production and oxygen consumption. In addition, PRRG4-mediated activation of STAT3 also enhanced filopodia formation, migration, and invasion of breast cancer cells. Moreover, PRRG4 elevated migratory behaviors and mitochondrial function of breast cancer cells through POLG.ConclusionOur results indicate that PRRG4 via the Src-STAT3-POLG axis enhances mitochondrial function and promotes migratory behaviors of breast cancer cells.

SOX10 promotes the malignant biological behavior of basal-like breast cancer cells by regulating EMT process

BackgroundThe diagnostic utility of SRY-box transcription factor 10 (SOX10) expression in basal-like breast cancer (BLBC) has been reported previously. However, the effect of SOX10 on the malignancy of BLBC cells and the underlying molecular mechanisms remain unelucidated. Here, we investigate the regulatory mechanisms and roles of SOX10 in BLBC progression. MethodsSequencing data from patients with BLBC were extracted from the Cancer Genome Atlas database to determine the transcriptomic levels of SOX10 across breast cancer subtypes. Subsequently, the bioinformatics relevance of SOX10 in BLBC was investigated. Immunohistochemical assays were used to corroborate the protein expression of SOX10 in clinicopathological specimens (human breast cancer paraffin tissues). RNA interference was used to downregulate SOX10 expression, and the efficiency of interference was evaluated using quantitative PCR. The expression levels of molecules related to the epithelial-mesenchymal transition (EMT) pathway were determined by western blotting. Various assays, such as transwell, colony formation, and flow apoptosis assays, were conducted to assess the malignancy of BLBC cells (MDA-MB-231). ResultsBioinformatics analyses revealed the differential expression of SOX10 in various breast cancer subtypes. An association between SOX10 and immune checkpoint expression was observed in BLBC. Additionally, immune correlation analysis indicated a positive relationship between SOX10 expression and effector immune cells. SOX10 was identified as a potential immunotherapeutic target. Juxtaposed with non-basal-like breast cancer (N-BLBC) and breast adenosis, immunohistochemical analysis revealed the upregulated expression of SOX10 in BLBC, indicating its potential diagnostic significance. Single-gene functional enrichment analysis indicated that SOX10 is associated with EMT and the tumor inflammatory index. Experimental outcomes from cellular assays suggested that the downregulation of SOX10 inhibited multiple malignancy-associated behaviors in MDA-MB-231 cells, specifically affecting the EMT process, migration, invasion, proliferation, clone formation, and anti-apoptotic activities. ConclusionsWe concluded that SOX10 contributes to the malignancy of BLBC cells by modulating the EMT pathway. Moreover, we observed a notable correlation between SOX10 expression and immune responses, indicating the potential significance of SOX10 in immunotherapy.

The effect of lactate dehydrogenase inhibitors on proliferation, motility and invasion of breast cancer cells invitro highlights a new role for lactate.

Lactate dehydrogenase (LDH) is being increasingly recognized as a major factor in the progression of breast cancer. It was previously shown that short interfering RNA‑mediated knockdown of either LDH‑A or ‑B isoform resulted in inhibition of cell motility due to reduced lactate levels in the extracellular environment. The aim of the present study was to determine the use of pharmacological LDH inhibitors to reduce aggressive behavior of breast cancer cells. The effect of LDH inhibitors was investigated in both estrogen receptor (ER)+ and ER‑ breast cancer cell lines and in normal breast epithelial cells. Cell proliferation, motility and invasion were measured using MTT, wound healing and cultrex assays, respectively. Changes in several key mediators of mitogenic signaling important in breast cancer cells were determined using western blotting. Treatment with various inhibitors reported to block LDH activity resulted in significant reduction in extracellular lactate level, cell proliferation, motility and invasion. This was associated with changes in the levels of vimentin, E‑cadherin, p38 MAPK, ERK1/2 and AKT. A couple of these inhibitors such as quercetin and lonidamine showed preferential inhibition of cancer cell proliferation compared with normal epithelial cell inhibition. These data extend initial findings, further underlining the importance of lactate as a major factor in breast cancer progression and indicate the practical use of various commercially available LDH inhibitors as promising therapeutic agents to oppose the processes leading to cancer progression.

Interaction of Graphene Oxide Particles and Dendrimers with Human Breast Cancer Cells by Real-Time Microscopy.

Graphene oxide (GOX) has become attractive due to its unique physicochemical properties. This nanomaterial can associate with other dendrimers, making them more soluble and allowing better interaction with biomacromolecules. The present study aimed to investigate, by real-time microscopy, the behavior of human breast cancer cells exposed to particles of materials based on graphene oxide. The MCF-7 cell line was exposed to GOX, GOX associated with Polypropylenimine hexadecaamine Dendrimer, Generation 3.0-DAB-AM-16 (GOXD) and GOX associated with polypropyleneimine-PAMAM (GOXP) in the presence or absence of fetal bovine serum (FBS). GOX, GOXD and GOXP were taken up by the cells in clusters and then the clusters were fragmented into smaller ones inside the cells. Real-time microscopy showed that the presence of FBS in the culture medium could allow a more efficient internalization of graphene materials. After internalizing the materials, cells can redistribute the clumps to their daughter cells. In conclusion, the present study showed that the particles can adhere to the cell surface, favoring their internalization. The presence of FBS contributed to the formation of smaller aggregates of particles, avoiding the formation of large ones, and thus transmitted a more efficient internalization of the materials through the interaction of the particles with the cell membrane.

A Novel Primary Cilium-Mediated Mechanism Through which Osteocytes Regulate Metastatic Behavior of Both Breast and Prostate Cancer Cells.

Bone metastases are a common cause of suffering in breast and prostate cancer patients, however, the interaction between bone cells and cancer cells is poorly understood. Using a series of co-culture, conditioned media, human cancer spheroid, and organ-on-a-chip experiments, this study reveals that osteocytes suppress cancer cell proliferation and increase migration via tumor necrosis factor alpha(TNF-α) secretion. This action is regulated by osteocyte primary cilia and associated intraflagellar transport protein 88 (IFT88). Furthermore, it shows that cancer cells block this mechanism by secreting transforming growth factor beta (TGF-β), which disrupts osteocyte cilia and IFT88 gene expression. This bi-directional crosstalk signaling between osteocytes and cancer cells is common to both breast and prostate cancer. This study also proposes that osteocyte inhibition of cancer cell proliferation decreases as cancer cells increase, producing more TGF-β. Hence, a positive feedback loop develops accelerating metastatic tumor growth. These findings demonstrate the importance of cancer cell-osteocyte signaling in regulating breast and prostate bone metastases and support the development of therapies targeting this pathway.

Hsa-miR-148a-3p promotes malignant behavior of breast cancer cells by downregulating DUSP1

To investigate the role of Hsa-miR-148a-3p in regulating biological behaviors of breast cancer cells and explore the mechanism. TCGA database was used to identify the differential miRNAs and mRNAs in breast cancer, and the protein-protein interaction (PPI) network was constructed using String and Cytoscape to screen the top 10 hub genes and construct the miRNA-TOP10hub network. RT-qPCR was used to detect the expressions of Hsa-miR-148a-3p and DUSP1 in breast cancer tissues and cell lines. The effects of Hsa-miR-148a-3p mimic and inhibitor on proliferation, migration, invasion and apoptosis of MCF-7 cells were analyzed, and luciferase reporter gene experiment was performed to verify the binding of Hsa-miR-148a-3p to DUSP1. The effect of Hsa-miR-148a-3p overexpression on breast cancer cell xenograft growth was evaluated in nude mice. Kaplan-Meier survival curve analysis was used to analyze the survival of the tumor-bearing mice, and the expression level of DUSP1 in the xenografts was detected using immunohistochemistry. A total of 54 differential miRNAs and 799 differential mRNAs were identified in breast cancer; 3716 target genes were intersected with the differential mRNA, resulting in 150 intersected genes. The top 10 hub genes were downregulated in breast cancer tissues in the PPI network. Double luciferase reporter gene experiment confirmed that Hsa-miR-148a-3p was capable of binding to DUSP1. Hsa-miR-148a-3p was up-regulated and DUSP1 was down-regulated significantly in breast cancer tissues and cells (P<0.01). In breast cancer cells, Hsa-miR-148a-3p mimic strongly promoted cell proliferation, migration and invasion and inhibited cell apoptosis (P<0.01). Hsa-miR-148a-3p overexpression obviously promoted xenograft growth in nude mice (P<0.01), shortened survival time of the mice (P<0.01), and reduced the expression of DUSP1 in the xenografts (P<0.01). Hsa-miR-148a-3p promotes malignant behavior of breast cancer cells by inhibiting the expression of DUSP1.

BTB protein family and human breast cancer: signaling pathways and clinical progress.

Breast cancer is considered the number one killer of women both in China and abroad, and the leading cause of cancer death. It severely affects female health-related quality of life. Broad-complex, tramtrack, bric à brac (BTB) protein family was first discovered in drosophila as early as in 1993 by Godt D and peers, since then, more family members and their critical biological functions were uncovered. Moreover, researchers around the world have recently demonstrated that numerous signaling pathways connect BTB family members and human breast cancer. In this review, we critically discuss these findings regarding the essential mechanisms and functions of the BTB protein family in mediating the organic processes of human breast cancer. Meanwhile, we summarize the signaling pathways the BTB protein family participates in. And we address that BTB proteins regulate the growth, apoptosis, and other behaviors of breast cancer cells. We also point out the future directions for further studies in this field. The relevant onlineliteratures have been reviewed for this article. This review could offer an update on novel molecular targets for treating human breast cancer and new insights into BTB protein family research.

Mechanism of Glucose Transporter Protein 1 Mediating Malignant Behavior in Breast Cancer Through the PI3K/Akt Signaling Pathway

To investigate the mechanism of action of GLUT1 in mediating breast cancer development through the PI3K/Akt signaling pathway. Knockdown of breast cancer cell line MDA-MB-231 GLUT1 was achieved by siRNA with the addition of IGF-1, an activator of the PI3K/AKT signaling pathway. The experimental groupings were NC, shGLUT1, shNC+IGF-1, and shGLUT1+IGF-1. The proliferation, invasion, and migration behaviors of breast cancer cells were observed by MTT, Transwell, and scratch-repair assays; Western blot was used to detect the protein expression levels of p-PI3K, p-AKT, and p-mTOR in the PI3K-AKT signaling pathway. After the knockdown of GLUT1, the expression levels of key proteins of the PI3K/AKT signaling pathway, p-PI3K, p-AKT, and p-mTOR, were significantly decreased. After the addition of IGF-1 alone, the decreasing trend of the protein expression levels of p-PI3K, p-AKT, and p-mTOR was even more pronounced, and the cellular functions of the cancer cells, such as proliferation and invasion, were also all inhibited. GLUT1 can promote breast cancer development through the PI3K/Akt signaling pathway.

Hsa-miR-497-3p impedes the proliferation and invasion of triple-negative breast cancer cells by controlling epithelial-mesenchymal transition through ZEB1 targeting.

This study aimed to examine the hsa-miR-497-3p effect and mechanism on the behavior of triple-negative breast cancer (TNBC) cells. We evaluated the expression of Hsa-miR-497-3p in tissue samples obtained from patients diagnosed with TNBC or luminal breast cancer (BrCa), utilizing the quantitative fluorescence polymerase chain reaction (PCR) method. We transfected hsa-miR-497-3p mimics and NC into MDA-MB-231 cells, whilehsa-miR-497-3p inhibitor and NC into TNBC cells, respectively. To examine the impact of hsa-miR-497-3p expression level on TNBC cell proliferation, invasion, and migration, we employed MTT, clone formation, Transwell, and wound healing assays. We utilized both q-PCR and western blot to validate the role of hsa-miR-497-3p in the epithelial-mesenchymal transition (EMT) of TNBC cells. To confirm the targeting relationship between hsa-miR-497-3p and ZEB1, we performed luciferase assays, q-PCR, and western blot analysis. We found that the hsa-miR-497-3p expression was down-regulated in both TNBC tissues and cell lines in comparison to luminal BrCa tissues and cell lines. Furthermore, hsa-miR-497-3p overexpression hindered the cell function of TNBC cells MDA-MB-231, while downregulating the mRNA and protein expression of vimentin and N-cadherin, while simultaneously upregulating E-cadherin expression. Our results demonstrate that hsa-miR-497-3p regulates EMT in TNBC cells through ZEB1 targeting, as evidenced by the modulation of the expression of vimentin, N-cadherin, and E-cadherin via ZEB1 inhibition. Overall, our study suggests that hsa-miR-497-3p inhibits the proliferation and invasion of TNBC cells through the modulation of EMT via ZEB1 targeting.