Tumor Cell Invasion Research Articles

Trends in Research of Odontogenic Keratocyst and Ameloblastoma.

Odontogenic keratocyst (OKC) and ameloblastoma (AM) are common jaw lesions with high bone-destructive potential and recurrence rates. Recent advancements in technology led to significant progress in understanding these conditions. Single-cell and spatial omics have improved insights into the tumor microenvironment and cellular heterogeneity in OKC and AM. Fibroblast subsets in OKC and tumor cell subsets in AM have been analyzed, revealing mechanisms behind their biological behaviors, including OKC's osteolytic features and AM's recurrence tendencies. Spatial transcriptomics studies of AM have identified engineered fibroblasts and osteoblasts contributing to matrix remodeling gene and oncogene expression at the invasion frontier, driving AM progression. Three-dimensional culture technologies such as organoid models have refined analysis of AM subtypes; uncovered the role of AM fibroblasts in promoting tumor cell proliferation and invasion; and identified signaling pathways such as FOSL1, BRD4, EZH2, and Wnt as potential therapeutic targets. Organoid models also served as preclinical platforms for testing potential therapies. Although preclinical models for AM exist, reliable in vitro and in vivo models for OKC remain scarce. Promising mimic models, including human embryonic stem cells-derived epithelial cells, human oral keratinocytes, human immortalized oral epithelial cells, and HaCaT keratinocytes, show promise, but the advancements in 3-dimensional culture technology are expected to lead to further breakthroughs in this area. Artificial intelligence, including machine learning and deep learning, has enhanced radiomics-based diagnostic accuracy, distinguishing OKC and AM beyond clinician capability. Pathomics-based models further predict OKC prognosis and differentiate AM from ameloblastic carcinoma. Clinical studies have shown positive outcomes with targeted therapies. In a study investigating SMO-targeted treatments for nevoid basal cell carcinoma syndrome, nearly all OKC lesions resolved in 3 patients. A recent clinical trial with neoadjuvant BRAF-targeted therapy for AM demonstrated promising radiologic responses, potentially enabling organ preservation. This review highlights recent advancements and trends in OKC and AM research, aiming to inspire further exploration and progress in these fields.

Polyoxometalate-based injectable coacervate inhibits HCC metastasis after incomplete radiofrequency ablation via scavenging ROS

BackgroundIncomplete radiofrequency ablation (iRFA) stimulates residual hepatocellular carcinoma (HCC) metastasis, leading to a poor prognosis for patients. Therefore, it is imperative to develop an effective therapeutic strategy to prevent iRFA-induced HCC metastasis.ResultsOur study revealed that iRFA induced an abnormal increase in ROS levels within residual HCC, which enhanced tumor cell invasiveness and promoted macrophage M2 polarization, ultimately facilitating HCC metastasis. Molybdenum-based polyoxometalate (POM) is an excellent ROS-scavenging nanocluster, but its size is too small to be easily cleared by the kidneys, limiting its effectiveness in scavenging iRFA-induced ROS. To overcome this limitation, we synthesized an injectable POM-loaded coacervate delivery system named POM@Coa, which can sustainably scavenge iRFA-induced ROS by slowly releasing POM. POM@Coa markedly reduced HCC invasiveness, reversed macrophage polarization from M2 to M1, and promoted the infiltration and activation of CD8+ T cells, ultimately inhibiting HCC metastasis. Importantly, POM@Coa showed superior therapeutic efficacy to free POM in the absence of systemic toxicity.ConclusionsPOM@Coa exhibits the potential to decrease HCC invasiveness and activate anti-tumor immunity, opening up new avenues for the safe and effective treatment and prevention of HCC metastasis when combined with RFA.

Cellular senescence in the tumor with a bone niche microenvironment: friend or foe?

Cellular senescence is understood to be a biological process that is defined as irreversible growth arrest and was originally recognized as a tumor-suppressive mechanism that prevents further propagation of damaged cells. More recently, cellular senescence has been shown to have a dual role in prevention and tumor promotion. Senescent cells carry a senescence-associated secretory phenotype (SASP), which is altered by secretory factors including pro-inflammatory cytokines, chemokines, and other proteases, leading to the alteration of the tissue microenvironment. Though senescence would eventually halt the growth of cancerous potential cells, SASP contributes to the tumor environment by promoting inflammation, matrix remodeling, and tumor cell invasion. The paradox of tumor prevention/promotion is particularly relevant to the bone niche tumor microenvironment, where longer-lasting, chronic inflammation promotes tumor formation. Insights into a mechanistic understanding of cellular senescence and SASP provide the basis for targeted therapies, such as senolytics, which aim to eliminate senescent cells, or SASP inhibitors, which would eliminate the tumor-promoting effects of senescence. These therapeutic interventions offer significant clinical implications for treating cancer and healthy aging.

ALB inhibits tumor cell proliferation and invasion by regulating immune microenvironment and endoplasmic reticulum stress in clear cell renal cell carcinoma.

The aim of this work is to identify putative hub genes for the advancement of clear cell renal cell carcinoma (ccRCC) and determine the fundamental mechanisms. We employed multiple bioinformatics techniques to screen hub genes. Key hub gene expression levels in ccRCC were assessed. A plethora of functional experiments were carried out to explore the biological role of hub gene. Based on genome-wide association studies, a Mendelian randomization research was conducted to ascertain the causative relationship between albumin (ALB) and ccRCC. ALB was low expression in ccRCC tissues and cell lines. It was an independent predictor of progression-free survival following treatment and the overall survival of ccRCC patients. ALB overexpression exhibited the reverse effects of ALB knockdown, which increased cell proliferation, migration, and invasion while inhibiting cell death. Similarly, ALB overexpression inhibited the growth of ccRCC tumors in vivo. Consistent with functional enrichment analysis, ALB overexpression activates the endoplasmic reticulum stress (ERS) in vitro and vivo. The Mendelian randomization showed ALB was associated with the risk of ccRCC. Additionally, ALB was causally associated with γδT cells infiltrates in ccRCC. ALB plays an important effect in ccRCC via activation of the ERS and regulating immune microenvironment.

Glut-1 exerts anti-tumor activity in glioma by regulating AKT / mTOR signaling pathway

Objective Glioma is a common tumor in neurosurgery. Glut-1 is the main carrier of glucose uptake by cells and can provide energy through the glycolytic pathway. However, the role and related mechanisms of Glut-1 in glioma have not yet been elucidated. Methods Real time PCR and Western blot were done to assess Glut-1 level in glioma tumor tissues and adjacent tissues. Glioma U87 cells were separated into control group; Glut-1 negative control (NC group); and Glut-1 siRNA group followed by analysis of Glut-1 expression, cell proliferation by MTT assay, cell invasion, cell apoptosis and cycle by flow cytometry and AKT / mTOR signaling proteins level by Western blot. Results Glut-1 expression was significantly increased in the tissues of glioma patients (P < 0.05) compared to adjacent tissues and its level was related to tumor size, pathological grade and survival. Down-regulating the expression of Glut-1 can significantly inhibit tumor cell proliferation and invasion, increase apoptosis and induce G0 phase of cell cycle arrest, and inhibit the expression of AKT / mTOR signaling proteins phosphorylation (P < 0.05). Conclusions Glut-1 level in glioma tissues is significantly increased, which is related to the pathological features. Down-regulating Glut-1 can inhibit glioma by regulating the AKT / mTOR signaling pathway.

MARVELD1 Promotes the Invasiveness in Pancreatic Adenocarcinoma through the Activation of Epithelial-to-Mesenchymal Transition.

MARVEL domain-containing 1 (MARVELD1) has been implicated in the progression of several cancers, but its role in pancreatic adenocarcinoma (PAAD) remains poorly understood. RNA-seq data from the TCGA-PAAD and GTEx-Pancreas cohorts were analyzed to assess MARVELD1 expression. Stable MARVELD1 knockdown and overexpression were conducted in BxPC3 and PANC-1 cells. Cell viability, proliferation, migration, and invasion were evaluated using functional assays, and western blotting was employed to examine EMT-associated protein levels, including Vimentin, MMP2, MMP9, and E-cadherin. Differentially expressed genes (DEGs) between MARVELD1-high and MARVELD1-low groups were identified, and pathway enrichment analyses were performed. We observed a significant increase of MARVELD1 in PAAD patient samples, with elevated MARVELD1 levels correlating with poor clinical survival. Knockdown of MARVELD1 in PAAD cells remarkably decreased cell proliferation and colony formation, while overexpression of MARVELD1 enhanced these properties. Moreover, simulated cell invasion and migration assay further suggested that MARVELD1 might contribute to PAAD cell aggressiveness. Mechanistically, MARVELD1 promoted tumor cell migration and invasion through the activation of Vimentin, MMP2, and MMP9 protein while suppressing E-cadherin. Bioinformatics analysis revealed that MARVELD1-high samples were enriched in EMT-related pathways, including TGF-β receptor signaling, actin cytoskeleton regulation, and cell adhesion. Taken together, our study highlights the roles of MARVELD1 in promoting tumor cell proliferation and invasion, suggesting its potential application as a prognostic and diagnostic biomarker for PAAD in the clinical context.

A Novel 167-Amino Acid Protein Encoded by CircPCSK6 Inhibits Intrahepatic Cholangiocarcinoma Progression via IKBα Ubiquitination.

Intrahepatic cholangiocarcinoma (ICC), a formidable challenge in oncology, demands innovative biomarkers and therapeutic targets. This research highlights the importance of the circular RNA (circRNA) circPCSK6 and its peptide derivative circPCSK6-167aa in ICC. CircPCSK6 is significantly downregulated in both ICC patients and mouse primary ICC models, and its lower expression is linked to adverse prognosis, highlighting its pivotal role in ICC pathogenesis. Functionally, this study elucidates the regulatory effect of circPCSK6-167aa on IκBα ubiquitination within the NF-κB pathway, which is mediated by its competitive binding to the E3 ligase RBBP6. This complex interaction leads to reduced activation of the NF-κB pathway, thereby curbing tumor cell proliferation, migration, invasion, stemness, and hepatic-lung metastasis in vivo. This groundbreaking discovery expands the understanding of circRNA-driven tumorigenesis through atypical signaling pathways. Additionally, this investigation identified EIF4A3 as a detrimental regulator of circPCSK6, exacerbating ICC malignancy. Importantly, by leveraging patient-derived xenograft (PDX), organoids, and organoid-derived PDX models, higher levels of circPCSK6-167aa enhance sensitivity to gemcitabine, indicating its potential to improve the effectiveness of chemotherapy. These insights emphasize the therapeutic promise of targeting circPCSK6-167aa, offering vital biological insights and clinical directions for developing cutting-edge therapeutic approaches, thus revealing innovative strategies and targets for future treatments.

Microenvironment Mechanical Torque from ZnFe2O4 (ZFO) Micromotors Inhibiting Tumor Migration.

Mechanical force attracts booming attention with the potential to tune the tumor cell behavior, especially in cell migration. However, the current approach for introducing mechanical input is difficult to apply in vivo. How the mechanical force affects cell behavior in situ also remains unclear. In this work, an intelligent miniaturized platform is constructed with magnetic ZnFe2O4 (ZFO) micromotors. The wireless ZFO can self-assemble in situ and rotate to generate mechanical torque of biologically relevant piconewton-scale at the target tumor site. It is observed unexpectedly that enhanced in situ mechanical rotating torque from ZFO micromotors and the active fluid inhibit the migration of highly invasive A549 tumor cells. The down-regulation of the Piezo1 channel and the suppressed signaling of ROCK1 in mechano-adaptive tumor cells is found to be related to the inhibition effect. With effectiveness confirmed with the zebrafish xenograft model, this platform provides a valuable toolkit for mechanobiology and force-associated non-invasive tumor therapy.

Targeting glycolysis: exploring a new frontier in glioblastoma therapy.

Glioblastoma(GBM) is a highly malignant primary central nervous system tumor that poses a significant threat to patient survival due to its treatment resistance and rapid recurrence.Current treatment options, including maximal safe surgical resection, radiotherapy, and temozolomide (TMZ) chemotherapy, have limited efficacy.In recent years, the role of glycolytic metabolic reprogramming in GBM has garnered increasing attention. This review delves into the pivotal role of glycolytic metabolic reprogramming in GBM, with a particular focus on the multifaceted roles of lactate, a key metabolic product, within the tumor microenvironment (TME). Lactate has been implicated in promoting tumor cell proliferation, invasion, and immune evasion. Additionally, this review systematically analyzes potential therapeutic strategies targeting key molecules within the glycolytic pathway, such as Glucose Transporters (GLUTs), Monocarboxylate Transporters(MCTs), Hexokinase 2 (HK2), 6-Phosphofructo-2-Kinase/Fructose-2,6-Biphosphatase 3 (PFKFB3), Pyruvate Kinase Isozyme Type M2 (PKM2), and the Lactate Dehydrogenase A (LDHA). These studies provide a novel perspective for GBM treatment. Despite progress made in existing research, challenges remain, including drug penetration across the blood-brain barrier, side effects, and resistance. Future research will aim to address these challenges by improving drug delivery, minimizing side effects, and exploring combination therapies with radiotherapy, chemotherapy, and immunotherapy to develop more precise and effective personalized treatment strategies for GBM.

Molecular mechanisms of transcription factor KLF4-mediated immune infiltration influencing lung adenocarcinoma invasion.

Lung adenocarcinoma (LUAD) is associated with an increasing incidence and mortality rate while existing treatment strategies continue to exhibit considerable limitation. Studies have demonstrated that upregulation of KLF4 gene inhibits LUAD progression, but its underlying mechanisms remain elusive. The present research explored roles and mechanisms of KLF4 and the NF-κB pathway in LUAD. Lentiviral vectors encoding KLF4 were constructed and transduced into H1299 and A549 cells to generate stable cell lines. These stable cell lines were then injected into BALB/c mice to establish a LUAD model. Subsequently, RNA sequencing, HE staining, immunohistochemistry, ELISA, Western blotting, and flow cytometry were employed to investigate the effects of KLF4 on tumor growth, invasion, immune cell infiltration, and related signaling pathways. Finally, dual-luciferase and in vivo mouse experiments were conducted to validate the molecular mechanisms. KLF4 significantly reduced tumor cell invasion while promoted tumor cell necrosis. Transcriptomic sequencing identified CXCR2 as a target gene and the NF-κB signaling pathway associated with immune infiltration regulation. KLF4 downregulated NF-κB2 and CXCR2 expression, concomitantly decreasing tumor cell invasiveness but increasing levels of CD4+ and CD8+ T cells and macrophages. NF-κB and CXCR2 play an important role in KLF4-mediated immune infiltration, thereby inhibiting tumor invasion and promoting tumor cell apoptosis in mice.

An integrated single-cell and spatial transcriptomic atlas of thyroid cancer progression identifies prognostic fibroblast subpopulations.

Thyroid cancer progression from curable well-differentiated thyroid carcinoma to highly lethal anaplastic thyroid carcinoma is distinguished by tumor cell de-differentiation and recruitment of a robust stromal infiltrate. Combining an integrated thyroid cancer single-cell sequencing atlas with spatial transcriptomics and bulk RNA-sequencing, we define stromal cell subpopulations and tumor-stromal cross-talk occurring across the histologic and mutational spectrum of thyroid cancer. We identify distinct inflammatory and myofibroblastic cancer-associated fibroblast (iCAF and myCAF) populations and perivascular-like populations. The myCAF population is only found in malignant samples and is associated with tumor cell invasion, BRAF V600E mutation, lymph node metastasis, and disease progression. Tumor-adjacent myCAFs abut invasive tumor cells with a partial epithelial-to-mesenchymal phenotype. Tumor-distant iCAFs infiltrate inflammatory autoimmune thyroid lesions and anaplastic tumors. In summary, our study provides an integrated atlas of thyroid cancer fibroblast subtypes and spatial characterization at sites of tumor invasion and de-differentiation, defining the stromal reorganization central to disease progression.

Clinical implications of epithelial-to-mesenchymal transition in cancers which potentially spread to peritoneum.

Epithelial-to-mesenchymal transition (EMT) is a biological process by which epithelial cells increase their motility and acquire invasive capacity. It represents a crucial driver of cancer metastasis and peritoneal dissemination. EMT plasticity, with cells exhibiting hybrid epithelial/mesenchymal states, and its reverse process, mesenchymal-to-epithelial transition (MET), allows them to adapt to different microenvironments and evade therapeutic intervention. Resistance to conventional treatments, including chemotherapy, is a major problem. Therapies targeting EMT may inhibit tumour cell migration and invasion, while affecting normal cells and repair mechanisms, resulting in potential side effects. This paper addresses the question of the impact of EMT status on cancers with potential spread to the peritoneum, which has remained unclear in literature. Relevant studies were selected from 2000 to 2024. Three macrosections were analysed: (i) pathological characteristics, (ii) surgical implications and (iii) oncological therapies. The focus was on survival and peritoneal recurrence time in patients who underwent surgical treatment.

Selenium-Chondroitin Sulfate Nanoparticles Inhibit Angiogenesis by Regulating the VEGFR2-Mediated PI3K/Akt Pathway.

Chondroitin sulfate (CS), a class of glycosaminoglycans covalently attached to proteins to form proteoglycans, is widely distributed in the extracellular matrix and cell surface of animal tissues. In our previous study, CS was used as a template for the synthesis of seleno-chondroitin sulfate (SeCS) through the redox reaction of ascorbic acid (Vc) and sodium selenite (Na2SeO3) and we found that SeCS could inhibit tumor cell proliferation and invasion. However, its effect on angiogenesis and its underlying mechanism are unknown. In this study, we analyzed the effect of SeCS on tube formation in vitro, based on the inhibition of tube formation and migration of human umbilical vein endothelial cells (HUVECs), and evaluated the in vivo angiogenic effect of SeCS using the chick embryo chorioallantoic membrane (CAM) assay. The results showed that SeCS significantly inhibited the angiogenesis of chicken embryo urothelium. Further mechanism analysis showed that SeCS had a strong inhibitory effect on VEGFR2 expression and its downstream PI3K/Akt signaling pathway, which contributed to its anti-angiogenic effects. In summary, SeCS showed good anti-angiogenic effects in an HUVEC cell model and a CAM model, suggesting that it may be a potential angiogenesis inhibitor.

MIRO2 promotes cancer invasion and metastasis via MYO9B suppression of RhoA activity.

Metastasis to vital organs remains the leading cause of cancer-related deaths, emphasizing an urgent need for actionable targets in advanced-stage cancer. The role of mitochondrial Rho GTPase 2 (MIRO2) in prostate cancer growth was recently reported; however, whether MIRO2 is important for additional steps in the metastatic cascade is unknown. Here, we show that knockdown of MIRO2 ubiquitously reduces tumor cell invasion invitro and suppresses metastatic burden in prostate and breast cancer mouse models. Mechanistically, depletion of MIRO2's binding partner-unconventional myosin 9B (MYO9B)-reduces tumor cell invasion and phenocopies MIRO2 depletion, which in turn results in increased active RhoA. Furthermore, dual ablation of MIRO2 and RhoA fully rescues tumor cell invasion, and MIRO2 is required for MYO9B-driven invasion. Taken together, we show that MIRO2 supports invasion and metastasis through cooperation with MYO9B, underscoring a potential targetable pathway for patients with advanced disease.

ZNF703 promotes Triple-Negative breast cancer cell progression and in combination with STK11 predicts disease recurrence (ZS -TNBC Model).

It is largely unidentified concerning the underlying genetic causes responsible for triple-negative breast cancers (TNBC), with unpredictable disease recurrence. This study aimed to examine the role of ZNF703 (Zinc finger 703) in the malignant behaviors of TNBC and its role in predicting disease-free survival (DFS). After downregulation of ZNF703 with short interfering RNA (siRNA), we examined the proliferation of TNBC cell line MDA-MB-231 by sulforhodamine B (SRB) assay, the invasion of cells by a transwell invasion model, and the migration of cells by the monolayer wound-healing experiment. mRNA-sequencing data of ZNF703, BRCA1, BRCA2, PALB2, CHEK2, CDH1, PTEN, STK11, ATM, and TP53, and corresponding clinical information were obtained from The Cancer Genome Atlas (TCGA) dataset for a total of 157 stage I-III TNBC samples. The selection of modeling features was executed using the Least Absolute Shrinkage and Selection Operator (LASSO) regression algorithm to avoid model overfitting. The TIMER 2.0 algorithm determined the associations between immune score and gene expressions. Kaplan-Meier analysis was conducted to plot survival analyses. The aggressive tumor morphology, cell proliferation, cell migration, and cell invasion were partly reversed by the siRNA knockdown of ZNF703 in MDA-MB-231 cells. ZNF703 knockdown markedly enhanced the killing ability of cisplatin These phenomena were verified by another TNBC cell line BT-549. Patients with high expression of ZNF703 had an inferior DFS for TNBC patients at 8years [Hazard ratio (HR) for high expression vs. low expression was 2.71; 95%CI, 1.03 to 7.14, P = 0.044]. Receiver Operating Characteristic (ROC) curve was also developed, indicating the area under the curve (AUC) was 0.744 (95%CI, 0.628 to 0.861) at 5years and 0.738 (95%CI, 0.552 to 0.924) at 8years, respectively. In addition, LASSO regression results showed that the optimal penalization parameter corresponds to two prognostic genes - ZNF703 and STK11. The risk score was computed as Risk Score (RS)=0.1033*ZNF703+0.2131*STK11 (named "ZS -TNBC model"). The high expression of both ZNF703 and STK11 had as high as 7.035 HR in comparison to the low-expression category (95%CI, 2.044 to 24.206, P = 0.00197). ZNF703 is required for the growth, invasion, and migratory behavior of TNBC cells. Downregulation of ZNF703 increases cisplatin efficacy. This study suggests that either ZNF703 alone or in conjunction with STK11 can be utilized to predict DFS in TNBC.

The Emerging Roles of CircPVT1 in Cancer Progression.

CircRNA is stable due to its ring structure and is abundant in humans, which not only exists in various tissues and biofluids steadily but also plays a significant role in the physiology and pathology of human beings. CircPVT1, an endogenous circRNA, has recently been identified from the PVT1 gene located in the cancer risk region 8q24. CircPVT1 is reported to be highly expressed in many different tumors, where it affects tumor cell proliferation, apoptosis, invasion, and migration. We summarize the biosynthesis and biological functions of circPVT1 and analyze the relationship between circPVT1 and tumors as well as its significance to tumors. Further, it's noteworthy for the diagnosis, treatment, and prognosis of cancer patients. Therefore, circPVT1 is likely to become an innovative tumor marker.

Modulation of the Oxygenation State and Intracellular pH of Erythrocytes by Inositol-Trispyrophosphate Investigated by 31P NMR Study of 2,3-DPG.

The hypoxic microenvironment is crucial for tumour cell growth and invasiveness. Tumour tissue results from adaptation to reduced oxygen availability. Hypoxia first activates pro-angiogenic signals for alleviation. Pathologic, tumour angiogenesis maintains hypoxia, impairing treatment outcomes. Vessel normalisation requires physioxia. Oxygen delivery by red blood cell (RBC) carrying haemoglobin (Hb) is enhanced by myo-inositol trispyrophosphate (ITPP), an effector of oxygen transport by RBCs. Altering glycolytic activity, it lowers intracellular pH and increases oxygen release from Hb. 31P NMR tracking of 2,3-diphosphoglycerate (2,3-DPG), allosteric effector of Hb and non-penetrating anion in RBCs, reports on erythrocytes internal environment. 31P resonances of 2,3-DPG are pH-sensitive, their positions indicate the oxygenation state of RBCs and interactions with effectors such as ITPP. Here we show invitro and invivo, that modifying Hb activity through band-3 anion transporter, ITPP enhances oxygen release and controls RBC internal pH. Its blood availability validates applicability of ITPP-based strategies.

High FGF18 expression levels predict poor prognosis in endometrial carcinoma patients and promote tumor growth and metastasis.

To investigate if fibroblast growth factor 18 (FGF18) expression plays an important role in endometrial carcinoma (EC). The clinicopathological associations and prognostic value of FGF18 expression were retrospectively analyzed in 190 patients with EC. FGF18 expression was stably knocked down in EC cell lines. Changes in cell proliferation, migration, and invasion rates were examined via cell behavior experiments. Tumor growth was investigated using a xenograft mouse model. RNA sequencing (RNA-seq) was performed to identify differentially expressed genes (DEGs) in HEC-1-B cells after FGF18 knockdown, followed by pathway enrichment analysis of the DEGs. High FGF18 expression levels were closely correlated with EC clinicopathological features, such as histological subtype, FIGO stage, depth of myometrial invasion, and tumor size. Moreover, EC patients with high FGF18 expression levels had poorer overall survival. FGF18 knockdown in EC cells revealed its role in promoting tumor cell proliferation, migration, and invasion in vitro, as well as tumor growth in vivo. RNA-seq of HEC-1-B cells revealed that the DEGs were enriched in signaling pathways related to cell proliferation and migration. Overexpression of FGF18 may serve as a prognostic biomarker for EC patients and is a potential therapeutic target for treating this disease.

Biomimetic celastrol nanocrystals with enhanced efficacy and reduced toxicity for suppressing breast cancer invasion and metastasis.

Breast cancer and its lung metastases pose significant threats to women's health worldwide, impacting their quality of life. Although several therapeutic strategies against breast cancer have been developed, they often cause serious side effects due to their high toxicity and low specificity. Therefore, novel therapeutic strategies that offer potent anti-tumor activity with minimal toxicity are urgently needed to combat the threat of breast cancer and lung metastases. Celastrol (Cela), a triterpenoid extracted from Tripterygium wilfordii, exerts anti-tumor effects by inhibiting tumor angiogenesis as well as tumor cell proliferation, invasion, and metastasis. However, its poor solubility and potential for severe organ toxicity hinder its clinical application. Therefore, in this study, we prepared Cela nanocrystals (Cela-NCs), which effectively increased the solubility of Cela and improved its bioavailability. Subsequently, Cela-NCs were encapsulated within the cell membrane (CCM) derived from breast cancer cells to generate CCM/Cela-NCs and leverage the homologous targeting ability of the CCM. Notably, CCM/Cela-NCs showed immune evasion and could homologously target tumor cells. Both in vitro and in vivo, CCM/Cela-NCs could effectively inhibit the growth and metastasis of breast cancer cells. They also exerted minimal hepatotoxicity in mice during treatment. In conclusion, this Cela-based biomimetic strategy that exploits the biological properties of tumor cells offers a new idea for the effective treatment of breast cancer and its lung metastasis.

Single-cell RNA-sequencing and spatial transcriptomic analysis reveal a distinct population of APOE- cells yielding pathological lymph node metastasis in papillary thyroid cancer.

Thyroid cancer is one of the most common endocrine tumors worldwide, especially among women and the metastatic mechanism of papillary thyroid carcinoma remains poorly understood. Thyroid cancer tissue samples were obtained for single-cell RNA-sequencing and spatial transcriptomics, aiming to intratumoral and antimetastatic heterogeneity of advanced PTC. The functions of APOE in PTC cell proliferation and invasion were confirmed through in vivo and in vitro assays. Pseudotime analysis and CellChat were performed to explore the the molecular mechanisms of the APOE in PTC progression. We identified a subpopulation of tumor cells with lower expression levels of APOE, associated with advanced stages of PTC and cervical metastasis. APOE overexpression significantly reduced tumor cell proliferation and invasion, both in vitro and in vivo, by activating the ABCA1-LXR axis. APOE- tumor cells may promote tumor growth by interacting with dendritic cells and CD4+ T cells via CD99- rather than CD6-regulated signaling. We established a machine learning-based scRNA-seq data, 13-gene signature predictive of lymph node metastasis. We identified a distinct APOE- tumor cell population associated with cervical metastasis and poor prognosis. Our results and models have potential clinical, prognostic, and therapeutic implications for advanced PTC. A subpopulation of tumor cells with lower expression levels of APOE was strongly associated with more advanced stages and metastasis of PTC. APOE-negative (APOE-) cellsoverall exhibited weaker interactions with immune cells. A machine-learning bioinformatics model based on scRNA-seq data of in-situ thyroid cancer tissue was established to predict lymph node metastasis.