Premium
Micro RNA ‐137‐mediated Src oncogenic signaling promotes cancer progression
Author(s) -
Kokuda Rie,
Watanabe Risayo,
Okuzaki Daisuke,
Akamatsu Hiroki,
Oneyama Chitose
Publication year - 2018
Publication title -
genes to cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.912
H-Index - 115
eISSN - 1365-2443
pISSN - 1356-9597
DOI - 10.1111/gtc.12610
Subject(s) - proto oncogene tyrosine protein kinase src , paxillin , downregulation and upregulation , biology , focal adhesion , protein kinase b , tumor progression , cancer research , microbiology and biotechnology , signal transduction , cancer , gene , biochemistry , genetics
Abstract The tyrosine kinase c‐Src is frequently overexpressed and activated in a wide variety of human cancers. However, the molecular mechanisms responsible for the upregulation of c‐Src remain elusive. To examine whether micro RNA ‐mediated c‐Src upregulation promotes cancer progression, we screened mi RNA s with complementarity to the 3′‐ UTR of c‐Src mRNA . Among these mi RNA s, down‐regulation of miR‐137 was tightly associated with c‐Src‐mediated tumor progression of human colon cancer cells/tissues. Re‐expression of miR‐137 in human colon cancer cells suppressed tumor growth and caused the disruption of focal contacts, suppression of cell adhesion, and invasion, although restoration of c‐Src in miR‐137‐treated cells could not fully rescue the tumor‐suppressive effect of miR‐137. We found that miR‐137 targets AKT 2 and paxillin also and miR‐137‐mediated regulation of c‐Src / AKT 2 is crucial for controlling tumor growth, whereas that of c‐Src/paxillin contributes to malignancy. miR‐137 suppressed Src‐related oncogenic signaling and changed the expression of mi RNA s that are regulated by Src activation. miR‐137 controls the expression of c‐Src/ AKT 2/paxillin and synergistically suppresses Src oncogenic signaling evoked from focal adhesions. In various human cancers that harbor c‐Src upregulation, the dysfunction of this novel mechanism would serve as a critical trigger for tumor progression.