TRPV4 Regulates Breast Cancer Cell Extravasation, Stiffness and Actin Cortex
| Autor: | Christian Harteneck, Vedula Sri Ram Krishna, Jean Paul Thiery, Tuan Zea Tan, Benedict Yan, Qingsong Lin, Patrick Tan, Lee Yee Choong, Ssu-Yi Lu, Martin Johansson, Yoon Pin Lim, Naing Naing Mon, Himanshu Singh, Brendan Pang, Chwee Teck Lim, Wen Hsin Lee |
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| Rok vydání: | 2016 |
| Předmět: |
Phosphopeptides
0301 basic medicine Pathology medicine.medical_specialty Lung Neoplasms Transplantation Heterologous Cell TRPV Cation Channels Breast Neoplasms Biology Article Disease-Free Survival Metastasis Mice 03 medical and health sciences Cell Movement Cancer stem cell Cell Line Tumor Cell cortex medicine Animals Humans RNA Messenger RNA Small Interfering Multidisciplinary Transendothelial and Transepithelial Migration Cancer medicine.disease Isogenic human disease models Extravasation Up-Regulation Transplantation Actin Cytoskeleton 030104 developmental biology medicine.anatomical_structure MCF-7 Cells Cancer research Calcium Female RNA Interference |
| Zdroj: | Scientific Reports |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/srep27903 |
| Popis: | Metastasis is a significant health issue. The standard mode of care is combination of chemotherapy and targeted therapeutics but the 5-year survival rate remains low. New/better drug targets that can improve outcomes of patients with metastatic disease are needed. Metastasis is a complex process, with each step conferred by a set of genetic aberrations. Mapping the molecular changes associated with metastasis improves our understanding of the etiology of this disease and contributes to the pipeline of targeted therapeutics. Here, phosphoproteomics of a xenograft-derived in vitro model comprising 4 isogenic cell lines with increasing metastatic potential implicated Transient Receptor Potential Vanilloid subtype 4 in breast cancer metastasis. TRPV4 mRNA levels in breast, gastric and ovarian cancers correlated with poor clinical outcomes, suggesting a wide role of TRPV4 in human epithelial cancers. TRPV4 was shown to be required for breast cancer cell invasion and transendothelial migration but not growth/proliferation. Knockdown of Trpv4 significantly reduced the number of metastatic nodules in mouse xenografts leaving the size unaffected. Overexpression of TRPV4 promoted breast cancer cell softness, blebbing, and actin reorganization. The findings provide new insights into the role of TRPV4 in cancer extravasation putatively by reducing cell rigidity through controlling the cytoskeleton at the cell cortex. |
| Databáze: | OpenAIRE |
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