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TGF β1‐induced cell motility but not cell proliferation is mediated through Cten in colorectal cancer
Author(s) -
Asiri Abdulaziz,
Raposo Teresa Pereira,
Alfahed Abdulaziz,
Ilyas Mohammad
Publication year - 2018
Publication title -
international journal of experimental pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.671
H-Index - 72
eISSN - 1365-2613
pISSN - 0959-9673
DOI - 10.1111/iep.12300
Subject(s) - tensin , downregulation and upregulation , focal adhesion , motility , epithelial–mesenchymal transition , cell growth , microbiology and biotechnology , transforming growth factor , gene knockdown , integrin , cell migration , cell , cancer research , signal transduction , cell adhesion , transforming growth factor beta , cell culture , biology , chemistry , pi3k/akt/mtor pathway , pten , biochemistry , genetics , gene
Summary Cten (C‐terminal tensin‐like) is a member of the tensin protein family found in complex with integrins at focal adhesions. It promotes epithelial‐mesenchymal transition ( EMT ) and cell motility. The precise mechanisms regulating Cten are unknown, although we and others have shown that Cten could be under the regulation of several cytokines and growth factors. Since transforming growth factor beta 1 ( TGF ‐β1) regulates integrin function and promotes EMT /cell motility, we were prompted to investigate whether TGF ‐β1 induces EMT and cell motility through Cten signalling in colorectal cancer. TGF ‐β1 signalling was modulated by either stimulation with TGF ‐β1 or knockdown of TGF ‐β1 in the CRC cell lines SW 620 and HCT 116. The effect of this modulation on expression of Cten, EMT markers and on cellular function was tested. The role of Cten as a direct mediator of TGF ‐β1 signalling was investigated in a CRC cell line in which the Cten gene had been deleted ( SW 620 ΔCten ). When TGF ‐β1 was stimulated or inhibited, this resulted in, respectively, upregulation and downregulation of Cten expression and EMT markers (Snail, Rock, N‐cadherin, Src). Cell migration and cell invasion were significantly increased following TGF ‐β1 stimulation and lost by TGF ‐β1 knockdown. TGF ‐β1 stimulation of the SW 620 ΔCten cell line resulted in selective loss of the effect of TGF ‐β1 signalling pathway on EMT and cell motility while the stimulatory effect on cell proliferation was retained. These data suggested Cten may play an essential role in mediating TGF ‐β1‐induced EMT and cell motility and may therefore play a role in metastasis in CRC .