Behavior Of Cancer Cells Research Articles

Post-Translational Modifications of Proteins Orchestrate All Hallmarks of Cancer.

Post-translational modifications (PTMs) of proteins dynamically build the buffering and adapting interface between oncogenic mutations and environmental stressors, on the one hand, and cancer cell structure, functioning, and behavior. Aberrant PTMs can be considered as enabling characteristics of cancer as long as they orchestrate all malignant modifications and variability in the proteome of cancer cells, cancer-associated cells, and tumor microenvironment (TME). On the other hand, PTMs of proteins can enhance anticancer mechanisms in the tumoral ecosystem or sustain the beneficial effects of oncologic therapies through degradation or inactivation of carcinogenic proteins or/and activation of tumor-suppressor proteins. In this review, we summarized and analyzed a wide spectrum of PTMs of proteins involved in all regulatory mechanisms that drive tumorigenesis, genetic instability, epigenetic reprogramming, all events of the metastatic cascade, cytoskeleton and extracellular matrix (ECM) remodeling, angiogenesis, immune response, tumor-associated microbiome, and metabolism rewiring as the most important hallmarks of cancer. All cancer hallmarks develop due to PTMs of proteins, which modulate gene transcription, intracellular and extracellular signaling, protein size, activity, stability and localization, trafficking, secretion, intracellular protein degradation or half-life, and protein-protein interactions (PPIs). PTMs associated with cancer can be exploited to better understand the underlying molecular mechanisms of this heterogeneous and chameleonic disease, find new biomarkers of cancer progression and prognosis, personalize oncotherapies, and discover new targets for drug development.

The impact of graphene oxide nanoparticles on the migratory behavior of metastatic human breast cancer cell, MDA-MB-231.

Breast cancer (BC) with aggressive metastasis is a serious ongoing public health problem among women. Graphene oxide (GO) has an inhibitory effect on the migration rate and metastasis of BC cells, but its various aspects have not yet been explored. This paper aims to research into the effect of GO nanoparticles (GO-Np) on the migratory behavior of MDA-MB-231 as a metastatic human BC cell line. We synthesized GO-Np using a modified Hummer's method. Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), dynamic light scattering (DLS) and zeta potential analyses were conducted to characterize GO-Np. Cytotoxicity of GO-Np against MDA-MB-231 cell lines was examined by optical microscopy and DAPI staining. Migration of cancer cells was analyzed by scratch healing test. Finally, the impact of GO-Np on the expression of BC markers, including Thrombospondin1 (THBS1) and Fibronectin1 (FN1) was investigated by Immunocytochemistry assay (ICC). Results showed a dose-dependent cytotoxicity of GO-Np to MDA-MB-231 cells. The half-maximal inhibitory concentration (IC50) of GO-Np was about 40 μg/ml based on both DAPI test and optical microscopy. The scratch healing test at IC50 concentration of GO-Np, showed a significant decrease (24.4%) in the migration percentage of cells compared to untreated cells. The ICC assay indicated that GO-Np can suppress the expression of both THBS1 and FN1, proving its anti-metastatic properties. In conclusion, GO-Np showed a promising anti-metastatic effect in MDA-MB-231 BC cells.

Oncogene OSTM1 Promotes Gastric-Cancer Metastasis by Modulating the Metastatic Microenvironment Through Altered Tumor-Cell Autocrine Signaling.

Gastric cancer remains a malignancy with high incidence, mortality rates, and poor prognosis globally. Osteoclastogenesis-associated transmembrane protein 1 (OSTM1), a transmembrane protein overexpressed in various tumors, has unclear functions in gastric-cancer progression. This study explores OSTM1's role in gastric-cancer proliferation and metastasis. OSTM1 expression was analyzed in gastric-cancer and adjacent tissues using immunohistochemistry and RT-qPCR. OSTM1 overexpression and knockdown cell lines were established to assess its effects on cancer-cell behavior through in vitro and in vivo experiments. Western blot and RT-qPCR were used to examine OSTM1's regulation of S100A4 expression. OSTM1 was significantly overexpressed in gastric-cancer tissues, negatively correlating with TNM staging and overall survival. OSTM1 overexpression enhanced cancer-cell proliferation, colony formation, migration, and invasion, while its knockdown showed opposite effects. In vivo studies confirmed increased lung metastatic capability in high OSTM1-expressing cells. Mechanistically, OSTM1 positively regulated S100A4 expression, with S100A4 knockdown reducing OSTM1-enhanced metastasis. Gastric-cancer lung metastases showed higher microvascular density and α-SMA-positive fibroblast infiltration in the OSTM1 high-expression group. OSTM1 promotes gastric-cancer progression by upregulating S100A4 and modifying the tumor microenvironment through enhanced angiogenesis and fibroblast activation. OSTM1 represents a potential diagnostic and prognostic biomarker, with the OSTM1-S100A4 axis offering new therapeutic possibilities for gastric-cancer treatment.

Endoglin as a predictive biomarker for pemetrexed sensitivity in non-small-cell lung cancer: a cellular study.

Based on our previous research, which demonstrated that elevated plasma endoglin (ENG) levels in lung cancer patients were associated with a better prognosis, increased sensitivity to pemetrexed, and enhanced tumor suppression, this study aims to validate these findings at the cellular level. The focus is on membrane and extracellular ENG and their influence on drug response and tumor cell behavior in non-small cell lung cancer (NSCLC) cells. The correlation between ENG expression and pemetrexed-induced cytotoxicity in eight human non-squamous subtype NSCLC cell lines was analyzed. ENG in A549 and H1975 cells was knocked down using shRNA. MTT assay, cell cycle assay, western blot analysis, and boyden chamber assay were used to detect the effect of ENG on pemetrexed-induced cytotoxicity, cell cycle distribution, and cell migration. The expression of membrane ENG was positively correlated with pemetrexed-induced cytotoxicity in human NSCLC cells. Compared to pemetrexed-sensitive A549 cells, the A549/a400 (pemetrexed-resistant subline) cells exhibited a reduced accumulation of cells in the S phase, making them less susceptible to cell death. ENG knockdown also alleviated pemetrexed-induced S phase arrest and regulated G1/S phase-related proteins (p53, p21, CDK2, and Cyclin A). Additionally, co-treatment with recombinant ENG enhanced pemetrexed-induced migration inhibition in the sensitive cel1 line and cytotoxicity in the resistance cell line. The present results strengthened our prior clinical findings, showing that higher membrane ENG expression enhances pemetrexed-induced cytotoxicity and S phase arrest, which may involve the ENG-p21 pathway. Additionally, microenvironmental ENG enhanced the anti-migration of pemetrexed. These findings highlight the potential of ENG as a biomarker and therapeutic target, opening new avenues to improve the outcomes of non-squamous cell NSCLC treatment.

Click Hydrogels to Assess Stiffness-Induced Activation of Pancreatic Cancer-Associated Fibroblasts and Its Impact on Cancer Cell Spreading.

Pancreatic ductal adenocarcinoma (PDAC) is marked by significant desmoplastic reactions, or the accumulation of excessive extracellular matrices. PDAC stroma has abnormally high stiffness, which alters cancer cell behaviors and creates a barrier for effective drug delivery. Unfortunately, clinical trials using a combination of chemotherapy and matrix-degrading enzyme have led to disappointing results, as the degradation of stromal tissue likely accelerated the dissemination of cancer cells. High matrix stiffness has been shown to activate cancer-associated fibroblasts (CAFs), increasing their interaction with pancreatic cancer cells (PCCs) through promoting proliferation, migration, and resistance to chemotherapy. With the advance of biomaterials science and engineering, it is now possible to design chemically defined matrices to understand the role of stiffness in activating pancreatic CAFs and how this may alter cancer cell migration. Here, we developed a norbornene-based click hydrogel system with independently tunable stiffness and cell adhesive ligand to evaluate stiffness-induced activation of CAFs and migration of PCCs. Our results show that matrix stiffness did not alter matrix deposition from CAFs but affected nuclear localization of Yes-associated protein (YAP). Our results also verify the role of CAFs on promoting PCC migration and an elevated substrate stiffness further increased PCC motility.

Mir-615-5p inhibits cervical cancer progression by targeting TMIGD2

BackgroundCervical cancer (CC) is a prevalent gynecological malignancy, contributing to a substantial number of fatalities among women. MicroRNAs (miRNAs) have emerged as promising biomarkers with significant potential for the early detection and prognosis of CC.ObjectiveThis study aimed to explore the clinical significance and biological role of miR-615-5p in CC, with the goal of identifying novel biomarkers for this disease.Materials and methodsThe levels of miR-615-5p and TMIGD2 mRNA in tissue samples and cells were quantified through quantitative reverse transcription real-time PCR, followed by statistical analyses to investigate the correlation between miR-615-5p and clinical data. The effects of miR-615-5p on the proliferation and metastasis of CC cells were evaluated using the Cell Counting Kit-8 and Transwell assays. The potential mechanism of miR-615-5p was elucidated by bioinformatics analyses and Dual-luciferase reporter assay. Western blotting was employed to measure the protein levels of TMIGD2.ResultsIn CC, the downregulation of miR-615-5p was related to poor prognosis and emerged as an independent prognostic factor. The levels of miR-615-5p were reduced in CC cells. miR-615-5p overexpression restrained the proliferation and metastasis of CC cells. Furthermore, TMIGD2 was identified as a target gene regulated by miR-615-5p, and its expression was notably elevated in CC. The influence of miR-615-5p on the biological behaviors of CC cells was mediated through the modulation of TMIGD2.ConclusionsDownregulation of miR-615-5p was a prognostic indicator of poor prognosis in CC. miR-615-5p exerted its tumor-suppressive effects by inhibiting cell growth and metastasis through the regulation of TMIGD2.

The effect of downregulation of ARL9 expression on the proliferation, metastasis and biological behavior of AGS gastric cancer cell lines.

Some ADP ribosylation factors (ARF) and ADP ribosylation factor-like (ARL) family are involved in the regulation of certain cancers, but the role of ADP ribosylation factor-like 9 (ARL9) in gastric tumorigenesis remains elusive. The main aim of this study was to evaluate the ARL9 expression within stomach cancer cells and elucidate its influence on the modulation of cancer cell behavior. Differential ARL9 protein expression in normal stomach and stomach cancer tissue was ascertained through data sourced from the University of Alabama at Birmingham Cancer Data Analysis Portal (UALCAN). Quantitative analysis of ARL9 expression in gastric cancer tissue and its association with clinicopathological features was performed using quantitative polymerase chain reaction (qPCR) and western blot analysis (WB). Small interfering RNA (siRNA) was employed to suppress ARL9 protein expression in the human stomach gastric adenocarcinoma human gastric adenocarcinoma cells (AGS) cell line. Assessment of AGS gastric cancer (GC) cell proliferation, invasion and migration was performed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and transwell techniques. The expression of ARL9 protein exhibited a significant upregulation in GC tissue, and showed a close association between tumor dimensions (p < 0.05) and the presence of distant metastases (p < 0.05) among individuals diagnosed with GC. However, no significant link was observed with sex, age and tumor-node-metastasis (TNM) staging in gastric malignancy patients. After the introduction of si-ARL9 in the experimental set, there was a noteworthy decrease in ARL9 protein levels in AGS cells (p < 0.01). In contrast to the control cohort, the restraint of ARL9 expression significantly hampered the growth, mobility and infiltration abilities of the AGS GC cell line (p < 0.01). The significant correlation of ARL9 with the biological behavior of GC indicates its potentially pivotal role in the pathophysiology of the malignancy.

The Emerging Role of Schwann Cells in the Tumor Immune Microenvironment and Its Potential Clinical Application.

As the primary glial cells in the peripheral nervous system (PNS), Schwann cells (SCs) have been proven to influence the behavior of cancer cells profoundly and are involved in cancer progression through extensive interactions with cancer cells and other stromal cells. Indeed, the tumor microenvironment (TME) is a critical factor that can significantly limit the efficacy of immunotherapeutic approaches. The TME promotes tumor progression in part by reshaping an immunosuppressive state. The immunosuppressive TME is the result of the crosstalk between the tumor cells and the different immune cell subsets, including macrophages, natural killer (NK) cells, dendritic cells (DCs), lymphocytes, myeloid-derived suppressor cells (MDSCs), etc. They are closely related to the anti-tumor immune status and the clinical prognosis of cancer patients. Increasing research demonstrates that SCs influence these immune cells and reshape the formation of the immunosuppressive TME via the secretion of various cytokines, chemokines, and other effector molecules, eventually facilitating immune evasion and tumor progression. In this review, we summarize the SC reprogramming in TME, the emerging role of SCs in tumor immune microenvironment, and the underlying mechanisms involved. We also discuss the possible therapeutic strategies to selectively target SCs, providing insights and perspectives for future research and clinical studies involving SC-targeted treatment.

GABPα targeted by miR-378a-5p inhibits the growth and angiogenesis of colorectal carcinoma.

Considering the high degree of malignancy, recurrence rate and poor prognosis, exploring promising targets is an imperious strategy for colorectal carcinoma therapy. Recent studies have indicated that GABPα plays a role in cancer aggressiveness, but its exact function and regulatory mechanisms in colorectal cancer progression remain unclear. This study aims to explore the biological role of GABPα and its upstream regulator, miR-378a-5p, in modulating cancer progression. The expression levels of GABPα and miR-378a-5p were analyzed through comprehensive data mining and qPCR assays. The functional effects of GABPα were assessed using CCK-8, wound healing, transwell invasion assay, tube formation and xenograft model in nude mice. A co-transfection assay was also performed to investigate the regulatory relationship between miR-378a-5p and GABPα. We found that GABPα expression was significantly downregulated in human colorectal cancer tissues and cell lines. Functional assays revealed that GABPα overexpression suppressed the proliferation, migration, invasion and angiogenesis of colorectal cancer cells, and in vivo experiments further confirmed the inhibitory role of GABPα. Additionally, miR-378a-5p was upregulated in colorectal cancer, and GABPα was identified as a direct target of miR-378a-5p, as confirmed by luciferase reporter assays. Furthermore, overexpression of GABPα partially counteracted the enhanced malignant behaviors of cancer cells induced by miR-378a-5p. Our findings suggest that miR-378a-5p promotes the aggressive progression of colorectal cancer by directly targeting GABPα, highlighting this regulatory axis as a potential therapeutic target for colorectal carcinoma.

Comprehensive pan-cancer analysis indicates UCHL5 as a novel cancer biomarker and promotes cervical cancer progression through the Wnt signaling pathway

BackgroundUCHL5 was initially recognized as a multifunctional molecule. While recent research has highlighted its involvement in tumor malignant biological behaviors, its specific role in promoting tumor cell apoptosis has drawn particular attention. However, the precise relationship between UCHL5 and various tumor types, as well as its influence within the immune microenvironment, remains unclear.MethodsThe transcriptomic data and clinicopathological parameters across 33 cancer types were obtained from TCGA. Clinical pathological parameters of tumor patients, including gender, age, survival time, and staging, are utilized to evaluate the association between UCHL5 and pan-cancer characteristics. The prognostic significance of UCHL5 was evaluated through Cox analysis and Kaplan-Meier (K-M) methods. Protein expression data for UCHL5 were obtained from The Human Protein Atlas database, and its subcellular localization was further investigated. Additionally, potential correlations between UCHL5 and factors such as tumor-infiltrating immune cells, immunomodulators, microsatellite instability (MSI), and tumor mutation burden (TMB) were explored. The relationship between UCHL5 and immunotherapy efficacy was also assessed in independent cohorts, including IMvigor210, GSE78220, GSE67501, and GSE168204. Finally, the impact of UCHL5 on the malignant biological behavior of cervical cancer cells was investigated through in vitro experiments, along with an exploration of the underlying mechanisms.ResultsWe observed that UCHL5 expression levels were elevated in 11 types of cancer tissues compared to their corresponding normal tissues, while levels were lower in five tumor types. Additionally, UCHL5 expression displayed a significant correlation with tumor stage in BRCA, KIRC, LUAD, and TGCT. Cox and K-M analysis indicated that UCHL5 expression was significantly associated with prognosis in KIRC, KICH, CESC, ACC, and UVM. UCHL5 expression was negatively associated with stromal and immune scores in certain cancers. In terms of immune cell infiltration, UCHL5 expression in UCEC, SKCM, and COAD showed a negative correlation with regulatory T cells (Tregs). Furthermore, UCHL5 was widely associated with three types of immunomodulators. It also demonstrated a significant relationship with MSI and TMB in certain cancers and was connected to the immunotherapy efficacy. Finally, in vitro experiments confirmed that UCHL5 knockout enhances apoptosis in cervical cancer cells and disrupts Wnt/β-catenin signaling.ConclusionsPan-cancer analysis indicates that UCHL5 is dysregulated in various tumor tissues and is closely associated with survival prognosis, the tumor immune microenvironment, and the efficacy of immunotherapy in certain cancer types. UCHL5 shows promise as a predictive biomarker, and its specific regulatory mechanisms across different cancers warrant further investigation.

Methyltransferase like 13 promotes malignant behaviors of bladder cancer cells through targeting PI3K/ATK signaling pathway.

Bladder cancer (BC) is the tenth most common tumor worldwide, characterized by high incidence rates and mortality. This study aimed to explore the role of Methyltransferase like 13 (METTL13) in BC cells. J82 and T24 cells were cultured for in vitro experiments. Cell viability, migration, and invasion were assessed using CCK-8 and transwell assays. Senescence-associated beta-galactosidase (SA-β-gal) levels were detected using a β-galactosidase staining kit. METTL13 and cell cycle-related protein levels were quantified using RT-qPCR and Western blotting. The results showed that METTL13 was upregulated in BC cells. Silencing METTL13 decreased cell viability, migration, and invasion in BC cells, whereas METTL13 overexpression increased these parameters. Additionally, METTL13 knockdown inhibited the phosphorylation levels of PI3K, AKT, and mTOR. Inhibition of the PI3K/AKT pathway reversed the effects of METTL13 on cell viability, migration, invasion, and cell cycle-related proteins in BC cells. In vivo experiments showed that METTL13 knockdown inhibited tumor growth and development. In conclusion, this study demonstrated that METTL13 promoted the malignant behaviors of BC cells through activation of the PI3K/AKT signaling pathway. METTL13 may be a promising therapeutic target for BC in the future.

NEK2 Phosphorylates RhoGDI1 to Promote Cell Proliferation, Migration and Invasion Through the Activation of RhoA and Rac1 in Colon Cancer Cells.

Rho guanine nucleotide dissociation inhibitor 1 (RhoGDI1) plays a critical role in regulating the activity of Rho guanosine triphosphatases (GTPases). Phosphorylation of RhoGDI1 dynamically modulates the activation of Rho GTPases, influencing cell proliferation and migration. This study explored the involvement of Never In Mitosis A (NIMA)-related serine/threonine protein kinase 2 (NEK2) in phosphorylating RhoGDI1 and its implications in cancer cell behavior associated with tumor progression. We employed GST pull-down assays and immunoprecipitation to investigate the interaction between NEK2 and RhoGDI1. Truncation fragments identified the region of RhoGDI1 responsible for binding with NEK2. Phosphorylation assays determined the site of NEK2-mediated phosphorylation on RhoGDI1. Functional assays were conducted using overexpression of the RhoGDI1 substitution mutant to assess their impact on cancer cell behavior. NEK2 directly bound to RhoGDI1 and phosphorylated it at Ser174. This phosphorylation event facilitated cancer cell proliferation and motility by activating RhoA and Rac1. The RhoGDI1 aa 112-134 region was critical for the binding to NEK2. Disruption of the NEK2-RhoGDI1 interaction through overexpression of a RhoGDI1 truncated fragment (aa 112-134) led to diminished RhoGDI1 phosphorylation and RhoA/Rac1 activation induced by NEK2, resulting in reduced cancer cell proliferation and migration. Moreover, in vivo studies showed reduced tumor growth and lung metastasis when the NEK2-RhoGDI1 interaction was disrupted. This study indicates that NEK2 promotes the metastatic behaviors of cancer cells by activating RhoA and Rac1 by phosphorylating RhoGDI1.

MiR-149-3p targeting TMPRSS4 regulates the sensitivity to cisplatin to inhibit the progression of lung cancer.

Lung cancer cells tend to develop resistance to cisplatin (DDP) during continuous chemotherapy, making it crucial to improve DDP sensitivity to enhance therapeutic outcomes. The levels of miR-149-3p in lung tissues and cells, as well as the biological behaviors of lung cancer cells, were analyzed. H446/DDP and A549/DDP cell lines were established to investigate how miR-149-3p affects lung cancer cells' sensitivity to DDP. Bioinformatics analysis predicted transmembrane serine protease 4 (TMPRSS4) as a downstream target of miR-149-3p, which was subsequently confirmed. Western blot analysis was used to examine proteins related to migration, invasion, apoptosis, and TMPRSS4 expression. Additionally, a subcutaneous graft tumor model in nude mice was created to assess the impact of miR-149-3p on tumor growth. In lung cancer tissues and cells, miR-149-3p expression was reduced, while TMPRSS4 expression was elevated. Overexpression of miR-149-3p inhibited cancer progression, promoted apoptosis, and enhanced the chemosensitivity of lung cancer cells to DDP. Moreover, miR-149-3p negatively regulated TMPRSS4, reducing malignancy-associated characteristics of lung cancer cells and further improving their DDP sensitivity. In vivo, high miR-149-3p expression increased the chemosensitivity of cancer cells. In conclusion, miR-149-3p suppresses the aggressive progression of lung cancer by directly downregulating TMPRSS4 and enhances the responsiveness of lung cancer cells to DDP.

A 3D-Printable Cell Array for In Vitro Breast Cancer Modeling.

Breast cancer is the most common cancer and the second leading cause of cancer-related death in women. In advanced stages of the disease, breast cancer can spread and metastasize to the bone, contributing to malignant progression. The roles of tissue stiffness and remodeling of the tumor microenvironment are relevant in influencing cancer progression and invasiveness, but they are still poorly understood. In this study, we aimed to investigate the effect of bone tissue stiffness on breast cancer cell behavior, using 3D cell-biomaterial systems to model the in vivo conditions. For this purpose, we developed a 3D-printable cell array, which is a tunable and reproducible platform on small scale, where each compartment could mimic the physiological cancer environment with a shape and rigidity close to bone tissue. In this system, we observed that in the highly metastatic breast cancer line MDA-MB-231, embedded in PEG-silk fibroin (PSF) hydrogel spheres in the array's cavities, increasing stiffness promotes trans-differentiation into osteoblast-like cells and the production of breast microcalcifications. Moreover, we also tested this 3D model as a platform to evaluate the cell response to the therapy, in particular, investigating the drug sensitivity of the cancer cells to chemotherapeutics, observing a decrease in drug resistance over time in the array.

MiR-379-5p affects breast cancer cell behavior by targeting UBE2E3 ubiquitin conjugating enzyme

MicroRNAs (miRNAs) play an increasingly recognized role in modulating cancer development. Due to their function in regulating gene expression, miRNAs can suppress or promote tumorigenesis. miR-379-5p expression is downregulated in multiple human cancers, including breast and bladder cancers. However, the mRNAs targeted by miR-379-5p that promote cancer development have not been fully identified. Our goal was to identify a gene whose expression is regulated by miR-379-5p, and which may contribute to cancer development in cells where miR-379-5p expression is reduced. Bioinformatics analysis showed the UBE2E3 ubiquitin conjugating enzyme gene to be a potential target for miR-379-5p. To verify that UBE2E3 is a target, we transfected normal human epithelial mammary cells and breast adenocarcinoma cell lines with a miR-379-5p mimic. The mimic reduced UBE2E3 mRNA and protein levels, as would be predicted for a miR-379-5p target. To determine if UBE2E3 is a direct target of miR-379-5p, we engineered two luciferase reporter gene constructs to contain either a wild-type putative miR-379-5p binding sequence isolated from the 3’UTR of the UBE2E3 gene, or a scrambled sequence. The luciferase assay showed that the miR-379-5p mimic suppressed luciferase activity for the WT binding sequence reporter, but not for the scrambled reporter, showing that the effect of miR-379-5p on UBE2E3 expression is likely to be direct. Finally, to determine if the effect of miR-379-5p on UBE2E3 is related to cellular behaviors that play a role in cancer development, we measured cell viability by resazurin assay, cell proliferation by BrdU assay, and apoptosis by caspase 3/7 activation assay. The miR-379-5p mimic and silencing UBE2E3 expression both resulted in significantly diminished cell viability, while silencing UBE2E3 demonstrated both higher proliferation and apoptotic rates. Overall, these results suggest that while the overall effect of miR-379-5p is to inhibit breast cell viability and proliferation, the effect of silencing its target UBE2E3 is more complex because it induces both cell proliferation and apoptosis.

Hypoglycemic Agents Increase Regulatory Factor X1 to Inhibit Cancer Cell Behaviour in Human Glioblastoma Cells.

Glioblastoma multiforme is a deadly brain tumour in humans. We have shown that regulatory factor X1 (RFX1), a transcription factor, inhibits the proliferation, migration and invasion of human glioblastoma cells. This study was designed to identify the existing medications that could increase RFX1 in human glioblastoma cells and to determine whether these medications could inhibit the cancer cell behaviours. A bioinformatics approach was used to identify the medications that increased RFX1. The effects of these medications on human glioblastoma cell proliferation, migration and invasion were assayed under cell culture and mouse brain xenograft conditions. Pioglitazone, rosiglitazone and WY-14643 increased RFX1 based on bioinformatics prediction and Western blotting data. These hypoglycemic agents reduced the proliferation, migration and invasion of human glioblastoma cell cultures. These agents reduced metalloproteinase 2 (MMP2) activity in the culture medium. Silencing RFX1 attenuated hypoglycemic agent-induced inhibition of cancer cell behaviours and MMP2 activity. Pioglitazone reduced the xenograft tumour volume and migration distance of U87 human glioblastoma cells in the mouse brain. RFX1-siRNA attenuated these effects. Our results provide additional evidence for RFX1 as a therapeutic target for human glioblastoma and suggest that pioglitazone, rosiglitazone and WY-14643 inhibit cancer cell behaviour of human glioblastoma cells via upregulating RFX1.

Comparative study of cytotoxic Signaling pathways in H1299 cells exposed to alternative Bisphenols: BPA, BPF, and BPS.

Bisphenols are prevalent in food, plastics, consumer goods, and industrial products. Bisphenol A (BPA) and its substitutes, bisphenol F (BPF) and bisphenol S (BPS), are known to act as estrogen mimics, leading to reproductive disorders, disruptions in fat metabolism, and abnormalities in brain development. Despite numerous studies exploring the adverse effects of bisphenols both in vitro and in vivo, the molecular mechanisms by which these compounds affect lung cells remain poorly understood. This study aims to compare the effects of BPA, BPF, and BPS on the physiological behavior of human nonsmall cell lung cancer (NSCLC) cells. Human non-small cell lung cancer (NSCLC) H1299 cells were treated with various concentration of BPA, BPF and BPS during different exposure time. Cellular physiology for viability and cell cycle was assessed by the staining with apoptotic cell makers such as active Caspase-3 and cyclins antibodies. Toxicological effect was quantitatively counted by using flow-cytometry analysis. Our findings indicate that BPA induces apoptosis by increasing active Caspase-3 levels in H1299 cells, whereas BPF and BPS do not promote late apoptosis. Additionally, BPA was found to upregulate cyclin B1, causing cell cycle arrest at the G0/G1 phase and leading to apoptotic cell death through Caspase-3 activation. Conclusion: These results demonstrate that BPA, BPF, and BPS differentially impact cell viability, cell cycle progression, and cell death in human NSCLC cells.

IGF2BPs-regulated TIN2 confers the malignant biological behaviors of gastric cancer cells

IGF2BPs-regulated TIN2 confers the malignant biological behaviors of gastric cancer cells

Quantification of the Most Effective X-Ray Dosage for Inhibiting Invasion of Glioma Cell Line.

One key feature that distinguishes cancerous cell populations from their normal counterparts is a heightened tendency towards uncontrolled growth and invasive activity. Therapeutic techniques like radiotherapy can impact the viability and invasive behavior of cancer cells by modifying the structure of DNA and inducing programmed cell death. This research is an experimental study and involved a comprehensive investigation into the effects of 6MV X-ray radiotherapy on various absorbed doses (ranging from 4 to 10 Gy by steps 2Gy) on toxicity, migration, and colony formation in C6 glioblastoma cellular cultures. Our detailed analysis revealed that the cytotoxic responses increased in a dose-dependent manner, while there was a significant decrease in both the ability to migrate and form colonies in the C6 cell line. This thorough examination provides new insights into the way malignant cell populations respond to ionizing radiation in a dose-dependent manner within a clinical setting. By directly impacting cellular functions and causing disturbances, this occurrence leads to a slowing down of disease progression.

Pyr3 inhibits cell viability and PKCα activity to suppress migration in human bladder cancer cells.

Bladder cancer, more prevalent in men, has high recurrence rates in non-muscle-invasive forms and is highly lethal upon metastasis in muscle-invasive cases. Transient receptor potential canonical channels (TRPCs), specifically TRPC3, play a role in calcium signaling, influencing cancer cell behavior. This study examines the effects of Pyr3, a TRPC3 inhibitor, and TRPC3 knockdown on both muscle-invasive (T24) and non-muscle-invasive (RT4) bladder cancer cells. Pyr3 treatment reduced cell viability, migration, adhesion, and calcium influx in these cells. Additionally, Pyr3 treatment and siTRPC3 downregulated protein kinase C alpha (PKCα), phospho-PKCα, and protein phosphatase 2A (PP2A) levels. While PKC activator phorbol 12-myristate 13-acetate (PMA) could not restore Pyr3-induced viability loss, it reversed the migration inhibition. In a xenograft model, Pyr3 suppressed T24 cell viability, Ki67, phospho-PKCα, PP2A and TRPC3 expression. These findings suggest that Pyr3 inhibits bladder cancer cell migration through PKC signaling and holds potential as a therapeutic agent for bladder cancer.