Please use this identifier to cite or link to this item: https://doi.org/10.1038/srep27903
Title: TRPV4 regulates breast cancer cell extravasation, stiffness and actin cortex
Authors: Lee, W.H 
Choong, L.Y 
Mon, N.N 
Lu, S 
Lin, Q 
Pang, B 
Yan, B
Krishna, V.S.R 
Singh, H
Tan, T.Z 
Thiery, J.P 
Lim, C.T 
Tan, P.B.O 
Johansson, M
Harteneck, C
Lim, Y.P 
Keywords: calcium
messenger RNA
phosphopeptide
small interfering RNA
vanilloid receptor
actin filament
animal
antagonists and inhibitors
breast tumor
cell motion
disease free survival
female
genetics
human
lung tumor
MCF-7 cell line
metabolism
mortality
mouse
pathology
RNA interference
secondary
transendothelial and transepithelial migration
tumor cell line
upregulation
xenograft
Actin Cytoskeleton
Animals
Breast Neoplasms
Calcium
Cell Line, Tumor
Cell Movement
Disease-Free Survival
Female
Humans
Lung Neoplasms
MCF-7 Cells
Mice
Phosphopeptides
RNA Interference
RNA, Messenger
RNA, Small Interfering
Transendothelial and Transepithelial Migration
Transplantation, Heterologous
TRPV Cation Channels
Up-Regulation
Issue Date: 2016
Citation: Lee, W.H, Choong, L.Y, Mon, N.N, Lu, S, Lin, Q, Pang, B, Yan, B, Krishna, V.S.R, Singh, H, Tan, T.Z, Thiery, J.P, Lim, C.T, Tan, P.B.O, Johansson, M, Harteneck, C, Lim, Y.P (2016). TRPV4 regulates breast cancer cell extravasation, stiffness and actin cortex. Scientific Reports 6 : 27903. ScholarBank@NUS Repository. https://doi.org/10.1038/srep27903
Abstract: 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.
Source Title: Scientific Reports
URI: https://scholarbank.nus.edu.sg/handle/10635/174007
ISSN: 20452322
DOI: 10.1038/srep27903
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