RRC ID 62731
Author Elmansuri AZ, Tanino MA, Mahabir R, Wang L, Kimura T, Nishihara H, Kinoshita I, Dosaka-Akita H, Tsuda M, Tanaka S.
Title Novel signaling collaboration between TGF-β and adaptor protein Crk facilitates EMT in human lung cancer.
Journal Oncotarget
Abstract The signaling adaptor protein Crk has been shown to play an important role in various human cancers. However, its regulatory machinery is not clear. Here, we demonstrated that Crk induced EMT in A549 human lung adenocarcinoma cells through differential regulation of Rac1/Snail and RhoA/Slug, leading to decreased expression of E-cadherin and increased N-cadherin, fibronectin, and MMP2 expression. Cancer cells with mesenchymal features produced TGF-β and also increased the levels of TGF-β receptor. TGF-β increased the endogenous levels of Crk and also augmented Crk-dependent expression of Snail and Slug, and conversely TGF-β receptor inhibitor suppressed the levels of Snail and Slug. Overexpression of Crk was observed at the invasive front of human lung cancer tissues and was significantly associated with poor prognosis. Thus, TGF-β and Crk collaborate to form a positive feedback loop to facilitate EMT, which may lead to the malignancy of human cancers possibly being affected by their microenvironment.
Volume 7(19)
Pages 27094-107
Published 2016-5-10
DOI 10.18632/oncotarget.8314
PII 8314
PMID 27027347
PMC PMC5053635
MeSH A549 Cells Animals Base Sequence Cell Line, Tumor Cells, Cultured Epithelial-Mesenchymal Transition / drug effects Epithelial-Mesenchymal Transition / genetics* Gene Expression Regulation, Neoplastic / drug effects HEK293 Cells Humans Lung Neoplasms / genetics* Lung Neoplasms / metabolism Lung Neoplasms / pathology Mice, Inbred BALB C Mice, Inbred NOD Mice, Nude Proto-Oncogene Proteins c-crk / genetics* Proto-Oncogene Proteins c-crk / metabolism Signal Transduction / drug effects Signal Transduction / genetics* Transforming Growth Factor beta / genetics* Transforming Growth Factor beta / metabolism Transforming Growth Factor beta / pharmacology Transplantation, Heterologous
IF 5.168
Human and Animal Cells 293T(RCB2202) A549