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Cten promotes Epithelial–Mesenchymal Transition (EMT) in colorectal cancer through stabilisation of Src
Author(s) -
Asiri Abdulaziz,
Toss Michael S.,
Raposo Teresa Pereira,
Akhlaq Maham,
Thorpe Hannah,
Alfahed Abdulaziz,
Asiri Abutaleb,
Ilyas Mohammad
Publication year - 2019
Publication title -
pathology international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.73
H-Index - 74
eISSN - 1440-1827
pISSN - 1320-5463
DOI - 10.1111/pin.12811
Subject(s) - proto oncogene tyrosine protein kinase src , gene knockdown , focal adhesion , epithelial–mesenchymal transition , cancer research , motility , metastasis , microbiology and biotechnology , oncogene , signal transduction , biology , cell , cancer , cell culture , cell cycle , biochemistry , genetics
Cten is an oncogene promoting EMT in many signaling pathways, namely through Snail. We investigated whether Cten function could be mediated through Src. Cten levels were modulated by forced expression in HCT116 and gene knockdown in SW620 CRC (colorectal cancer) cell lines. In all cell lines, Cten was a positive regulator of Src expression. The functional importance of Src was tested by simultaneous Cten overexpression and Src knockdown. This resulted in abrogation of Cten motility‐inducing activity and reduction of colony formation ability together with failure to induce Cten targets. In SW620 ΔCten reduced Src expression increased following restoration of Cten, also leading to increased cell motility and colony formation, which were lost if Src was concomitantly knocked down. By qRT‐PCR we showed modulation of Cten had no effect on Src mRNA. However, a CHX pulse chase assay demonstrated stabilization of Src protein by Cten. Finally, expression of Cten and Src was tested in a series of 84 primary CRCs and there was a significant correlation between them ( P = 0.001). We conclude that Src is a novel and functionally important target of the Cten signaling pathway and that Cten protein causes post‐transcriptional stabilization of Src in promoting EMT and possibly metastasis in CRC.