Mechanosensitive TRPV4 Trafficking Drives TGF-Β-Mediated Mesenchymal Transition in Colorectal Cancer DOI Open Access
Caner Karaca, Yasemin Başbınar

Journal of Basic and Clinical Health Sciences, Journal Year: 2025, Volume and Issue: 9(1), P. 218 - 229

Published: Jan. 31, 2025

Background and Purpose Epithelial-to-mesenchymal transition (EMT) enhances the invasive potential of cancers, significantly affecting survival rates in metastatic disease. TGF-β, a potent EMT regulator enriched colon cancer (CRC), is influenced by bioelectric biophysical forces. While some ion channels mechanical forces are linked, TGF-β-coupled mechanosensing mechanisms CRC remain poorly understood. This study investigates mechanosensitive channel TRPV4 its role TGF-β-induced EMT, focusing on trafficking functional implications CRC. Methods We analyzed mRNA expressions stages evaluated their association with through Kaplan-Meier analysis. Correlations were mesenchymal gene sets, soluble factors, TGF-β signaling. Immunofluorescence was used to visualize localization untreated 10 ng/mL TGF-β1-treated cell lines. Functional studies involved co-stimulation TGF-β1 modulators (GSK101 HC-067047) assess EMT-related changes. Results elevated CRC, TRPV4-001 as predominant isoform. High expression correlated poor survival, signatures, signaling . induced out-of-nucleus translocation. inhibition reduced N-cadherin expression, mitigating EMT. Conclusion regulates mechanisms. Its presents anti-metastatic potential, identifying therapeutic target

Language: Английский

Prognostic impact of glucagon-like peptide-1 receptor (GLP1R) expression on cancer survival and its implications for GLP-1R agonist therapy: an integrative analysis across multiple tumor types DOI Creative Commons
Zoltán Ungvári, Áron Bartha, Anna Ungvari

et al.

GeroScience, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 8, 2025

Language: Английский

Citations

2
Noncanonical UPR factor CREB3L2 drives immune evasion of triple-negative breast cancer through Hedgehog pathway modulation in T cells DOI Creative Commons

Zi-Jian Cao,

Jia You,

Yu-Meng Fan

et al.

Science Advances, Journal Year: 2025, Volume and Issue: 11(2)

Published: Jan. 10, 2025

The unfolded protein response (UPR) pathway is crucial for tumorigenesis, mainly by regulating cancer cell stress responses and survival. However, whether UPR factors facilitate cell-cell communication between cells immune to drive progression remains unclear. We found that adenosine 3′,5′-monophosphate element–binding 3–like 2 (CREB3L2), a noncanonical factor, overexpressed activated in triple-negative breast cancer, where its cleavage releases C-terminal fragment activates the Hedgehog neighboring CD8+ T cells. enhanced represses activation inhibits cytotoxic effects. Consequently, overexpression of CREB3L2 not only promotes tumor growth but also causes resistance checkpoint blockade (ICB). Inhibition impedes CREB3L2-overexpressed tumors sensitizes them ICB therapy. In summary, we identified previously unidentified mechanism which dictates cross-talk cells, providing important anticancer therapeutic opportunities.

Language: Английский

Citations

1
Combined MDM2 and G2/M checkpoint inhibition induces synergistic antitumor response in gastric signet-ring cell carcinoma DOI

Dandong Luo,

Huashe Wang,

Jun Liu

et al.

Cancer Letters, Journal Year: 2025, Volume and Issue: 613, P. 217500 - 217500

Published: Jan. 31, 2025

Language: Английский

Citations

1
Association of NR0B1 with Malignant Phenotypes in Esophageal Squamous Cell Carcinoma Through Modulation of p53-Independent Cell-Cycle Regulation DOI

Akimitsu Iizuka,

Mitsuro Kanda,

Yusuke Sato

et al.

Annals of Surgical Oncology, Journal Year: 2025, Volume and Issue: unknown

Published: March 13, 2025

Language: Английский

Citations

1
Estrogen receptors and extracellular matrix: the critical interplay in cancer development and progression DOI Creative Commons

Sylvia Mangani,

Zoi Piperigkou,

Nikolaos E. Koletsis

et al.

FEBS Journal, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 16, 2024

Cancer remains a significant global health concern. Breast cancer is multifaceted and prevalent disease influenced by several factors, among which estrogen receptors (ERs) the extracellular matrix (ECM) play pivotal roles. ERs, encompassing ERα ERβ, exert diversity on tumor behavior, cell signaling, invasion, metastatic potential, thus guiding breast prognosis. Understanding multifunctional connections between ERs ECM that mediate dynamics of microenvironment vital for unraveling complexity pathobiology identifying novel therapeutic targets. This critical review delves into intricate nature emphasizing their structural isoforms consequential impact outcomes. A detailed examination ER‐mediated signaling pathways reveals how differential expression ERβ influence behavior. The functional ERs‐matrix interactions emerge as factor in modulating epigenetic mechanisms cells, orchestrating changes cellular phenotype patterns modulators. Specifically, are shown to regulate cascades, while effects components activity highlight bidirectional regulatory axis. also highlighted, illustrating distinct contribution ECM‐mediated responses. underscores complex interplay ERα/β ECM, shedding light onto potential strategies targeting these improve management.

Language: Английский

Citations

6
Expression Profiles of Dopamine-Related Genes and miRNAs Regulating Their Expression in Breast Cancer DOI Open Access

Tomasz Sirek,

Agata Sirek,

Przemysław Borawski

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(12), P. 6546 - 6546

Published: June 14, 2024

This study aimed to assess the expression profile of messenger RNA (mRNA) and microRNA (miRNA) related dopaminergic system in five types breast cancer Polish women. Patients with subtypes were included study: luminal A (n = 130), B 196, including HER2−, n 100; HER2+, 96), HER2+ 36), TNBC 43); they underwent surgery, during which tumor tissue was removed along a margin healthy (control material). The molecular analysis microarray mRNAs miRNAs associated system, real-time polymerase chain reaction preceded by reverse transcription for selected genes, determinations their concentration using enzyme-linked immunosorbent assay (ELISA). conducted statistical showed that statistically significantly differentiated sections regardless subtype compared control samples; these dopamine receptor 2 (DRD2), 3 (DRD3), 25 (DRD5), transforming growth factor beta (TGF-β-2), caveolin (CAV2). predicted hsa-miR-141-3p can regulate DRD2 TGF-β-2, whereas hsa-miR-4441 is potentially engaged regulation DRD3 DRD5. In addition, pattern DRD5 mRNA also be regulated has-miR-16-5p. overexpression DRD3, concomitant silencing expression, confirms presence abnormalities patients. Moreover, may result miR-141-3P, miR-16-5p, miR-4441 activity, regulating proliferation or metastasis.

Language: Английский

Citations

5
Combination therapy with Chicoric acid and PD-1/PD-L1 blockade improves the immunotherapy response in patient-derived ovarian cancer xenograft model DOI Creative Commons

Hongwei Lan,

Jingjuan Zhu,

Helei Hou

et al.

Cell Communication and Signaling, Journal Year: 2025, Volume and Issue: 23(1)

Published: March 14, 2025

Limited treatment options exist for refractory ovarian cancer (OC) due to its poor response immune therapies. Therefore, there is an urgent need develop new effective strategies. Chicoric acid (CA) reported have immune-enhancing properties, but efficacy in not well understood. We hypothesize that CA might improve the of PD-1/PD-L1 blockade immunotherapy OC patients. Patient-derived xenograft (PDX) models were constructed from chemoresistant advanced high-grade serous These treated with CA, aPD-1/aPD-L1 antibodies, or a combination both. Single-cell RNA sequencing was performed analyze cellular composition tumor microenvironment (TME), evaluate efficacy, and explore therapeutic mechanisms. Variations peripheral blood lymphocytes analyzed via fluorescence-activated cell sorting. Immunohistochemistry confirmed variations tumor-infiltrating cells. Immunocompetent mononuclear (PBMC)-PDX successfully using malignant ascites fluid PBMCs. After treatment, 158,734 cells 15 samples categorized into epithelial cells, T lymphocytes, myeloid fibroblasts, endothelial enhanced antitumor ability against Notably, stimulated proliferation CD45 + CD3 promoted migration CD8 CD4 infiltrate TME. Additionally, OCs aPD-L1/aPD-1 strengthened interaction between nontumor identified APP/CD74 as critical ligand‒receptor pair. CHI3L1 also found be potential marker predicting OC. This study demonstrated therapy promising strategy treating effectively.

Language: Английский

Citations

0
AGO2 mediates immunotherapy failure via suppressing tumor IFN-gamma response-dependent CD8+ T cell immunity DOI
Yuzhao Wang, Zibin Chen, Ke Liang

et al.

Cell Reports, Journal Year: 2025, Volume and Issue: 44(4), P. 115445 - 115445

Published: March 18, 2025

Language: Английский

Citations

0
Arginase-II promotes melanoma and lung cancer cell growth by regulating Sirt3-mtROS axis DOI Creative Commons
Yang Yang, Andrea Brenna, Duilio Michele Potenza

et al.

Frontiers in Cell and Developmental Biology, Journal Year: 2025, Volume and Issue: 13

Published: March 19, 2025

Background Aberrant mitochondrial metabolism is a key source of massive reactive oxygen species (mtROS) in tumour cells. Arginase-II (Arg-II), widely expressed metabolic enzyme, has recently been shown to enhance mtROS production and melanoma progression. However, how Arg-II enhances whether involved stimulation cancer cell proliferation migration remain unclear. Methods results Here, we show that ablation arg-ii suppresses growth, migration, nuclear deformation, DNA damage Vice versa, overexpression cells promotes growth accompanied by enhanced deformation damage. Ablation or reduces mtROS, respectively, accounting for the effects on Further data demonstrate through decreasing Sirtuin 3 (Sirt3) levels. Silencing sirt3 enhancing mtROS. In supporting these findings, prevented Arg-II-induced with concomitant prevention Furthermore, upregulation under hypoxia induces suppressing Sirt3. Similar are obtained A549 human lung carcinoma addition, analysis publicly accessible datasets reveals elevated mRNA levels tumor samples including skin cutaneous cancers associate poorer prognosis. Conclusion Altogether, our findings critical role Arg-II-Sirt3-mtROS cascade promoting linking progression malignancy, which could be therapeutic targets such as carcinoma.

Language: Английский

Citations

0
Integrating network pharmacology to investigate the mechanism of quercetin's action through AKT inhibition in co-expressed genes associated with polycystic ovary syndrome and endometrial cancer DOI
Mengyuan Li,

Yewei Cui,

Xue‐Ru Wu

et al.

International Journal of Biological Macromolecules, Journal Year: 2025, Volume and Issue: 297, P. 139468 - 139468

Published: Jan. 5, 2025

Language: Английский

Citations

0