| RRC ID |
62731
|
| 著者 |
Elmansuri AZ, Tanino MA, Mahabir R, Wang L, Kimura T, Nishihara H, Kinoshita I, Dosaka-Akita H, Tsuda M, Tanaka S.
|
| タイトル |
Novel signaling collaboration between TGF-β and adaptor protein Crk facilitates EMT in human lung cancer.
|
| ジャーナル |
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.
|
| 巻・号 |
7(19)
|
| ページ |
27094-107
|
| 公開日 |
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
|
| リソース情報 |
| ヒト・動物細胞 |
293T(RCB2202)
A549 |
