ArticleMolecular cancer2015
Invasion of ovarian cancer cells is induced byPITX2-mediated activation of TGF-β and Activin-A.
Article in Molecular cancer, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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50 citing papers in PubMed, 70 citations in OpenAlex.
- Spatially resolved single cell atlas deciphers SAA1 inflammatory epithelial cells.International journal of oral science · 2026Article
- A Distal Super-Enhancer Regulates CD47 Expression and Promotes Macrophage-Mediated Phagocytosis of Ovarian Cancer Cells.bioRxiv : the preprint server for biology · 2026Article
- Prognostic influence of small leucine-rich proteoglycans on serous ovarian cancer.Journal of cancer research and clinical oncology · 2026Article
- A comprehensive review of the emerging role of NRF3 in ovarian cancer tumorigenesis and progression.Journal of ovarian research · 2026Review
- Nortriptyline Inhibits Lysosomal Exocytosis-Mediated SASP During Gastric Cancer Progression via Targeting HOXA1-PITX2 Phase Separation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- The roles of TGF-β, Wnt, and MAPK signaling pathways in joint lineage specification in vitro and ex vivo.Stem cell reports · 2025Article
- Tumor location, genomic alterations, and radiomic features as predictors of survival in glioblastoma: a Multi-Modal analysis.Neuroradiology · 2025Article
- Knockdown of Inhibin Beta A Reversed the Epithelial Growth Factor Receptor Tyrosine Kinase Inhibitor Resistance and Enhanced the Therapeutic Effect of Radiotherapy in Non-Small Cell Lung Cancer.Biochemical genetics · 2025Article
- Multi‑omics identification of a novel signature for serous ovarian carcinoma in the context of 3P medicine and based on twelve programmed cell death patterns: a multi-cohort machine learning study.Molecular medicine (Cambridge, Mass.) · 2025Article
- Alternative splicing in ovarian cancer.Cell communication and signaling : CCS · 2024Review
- Activin A plays an essential role in migration and proliferation of hepatic stellate cells via Smad3 and calcium signaling.Scientific reports · 2024Article
- Epicardial EMT and cardiac repair: an update.Stem cell research & therapy · 2024Review
- INHBA(+) cancer-associated fibroblasts generate an immunosuppressive tumor microenvironment in ovarian cancer.NPJ precision oncology · 2024Article
- Modelling the complex nature of the tumor microenvironment: 3D tumor spheroids as an evolving tool.Journal of biomedical science · 2024Review
- Presence of onco-fetal neighborhoods in hepatocellular carcinoma is associated with relapse and response to immunotherapy.Nature cancer · 2024Article
- PITX2 in pancreatic stellate cells promotes EMT in pancreatic cancer cells via the Wnt/β-catenin pathway.Acta biochimica et biophysica Sinica · 2023Article
- Histone Modifications Represent a Key Epigenetic Feature of Epithelial-to-Mesenchyme Transition in Pancreatic Cancer.International journal of molecular sciences · 2023Review
- PITX2C increases the stemness features of hepatocellular carcinoma cells by up-regulating key developmental factors in liver progenitor.Journal of experimental & clinical cancer research : CR · 2022Article
- Novel Inhibitor for Downstream Targeting of Transforming Growth Factor-β Signaling to Suppress Epithelial to Mesenchymal Transition and Cell Migration.International journal of molecular sciences · 2022Article
- Review
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundMost ovarian cancers are highly invasive in nature and the high burden of metastatic disease make them a leading cause of mortality among all gynaecological malignancies. The homeodomain transcription factor, PITX2 is associated with cancer in different tissues. Our previous studies demonstrated increased PITX2 expression in human ovarian tumours. Growing evidence linking activation of TGF-β pathway by homeodomain proteins prompted us to look for the possible involvement of this signalling pathway in PITX2-mediated progression of ovarian cancer.
methodsThe status of TGF-β signalling in human ovarian tissues was assessed by immunohistochemistry. The expression level of TGFB/INHBA and other invasion-associated genes was measured by quantitative-PCR (Q-PCR) and Western Blot after transfection/treatments with clones/reagents in normal/cancer cells. The physiological effect of PITX2 on invasion/motility was checked by matrigel invasion and wound healing assay. The PITX2- and activin-induced epithelial-mesenchymal transition (EMT) was evaluated by Q-PCR of respective markers and confocal/phase-contrast imaging of cells.
resultsHuman ovarian tumours showed enhanced TGF-β signalling. Our study uncovers the PITX2-induced expression of TGFB1/2/3 as well as INHBA genes (p < 0.01) followed by SMAD2/3-dependent TGF-β signalling pathway. PITX2-induced TGF-β pathway regulated the expression of invasion-associated genes, SNAI1, CDH1 and MMP9 (p < 0.01) that accounted for enhanced motility/invasion of ovarian cancers. Snail and MMP9 acted as important mediators of PITX2-induced invasiveness of ovarian cancer cells. PITX2 over-expression resulted in loss of epithelial markers (p < 0.01) and gain of mesenchymal markers (p < 0.01) that contributed significantly to ovarian oncogenesis. PITX2-induced INHBA expression (p < 0.01) contributed to EMT in both normal and ovarian cancer cells.
conclusionsOverall, our findings suggest a significant contributory role of PITX2 in promoting invasive behaviour of ovarian cancer cells through up-regulation of TGFB/INHBA. We have also identified the previously unknown involvement of activin-A in promoting EMT. Our work provides novel mechanistic insights into the invasive behavior of ovarian cancer cells. The extension of this study have the potential for therapeutic applications in future.
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