原肌球蛋白受体激酶C
生物
癌症研究
受体酪氨酸激酶
分子生物学
低亲和力神经生长因子受体
细胞生物学
信号转导
神经营养素
受体
血小板源性生长因子受体
生物化学
生长因子
作者
Wook Jin,Chohee Yun,M-K Kwak,T-A Kim,Sung‐Jae Kim
出处
期刊:Oncogene
[Springer Nature]
日期:2007-06-04
卷期号:26 (55): 7684-7691
被引量:27
标识
DOI:10.1038/sj.onc.1210571
摘要
Growing evidence suggests that overexpression of TrkC, a member of the Trk family of neurotrophin receptors, could drive tumorigenesis, invasion and metastatic capability in cancer cells. However, relatively little is known about the mechanism of TrkC-mediated oncogenesis. The TrkC gene is a partner of the Tel-TrkC (ETV6-NTRK3) chimeric tyrosine kinase, a potent oncoprotein expressed in tumors derived from multiple cell lineages. Recently, we have shown that ETV6-NTRK3 suppresses transforming growth factor-β (TGF-β) signaling by directly binding to the type II TGF-β receptor (TβRII). Here, we report that expression of TrkC also suppresses TGF-β-induced Smad2/3 phosphorylation and transcriptional activation. Silencing TrkC expression by small interfering RNA in the highly metastatic 4T1 mammary tumor cell line expressing endogenous TrkC significantly enhanced TGF-β-induced Smad2/3 phosphorylation and restored TGF-β growth inhibitory activity. In contrast, expression of TrkC in 67NR cells, in which TrkC is not expressed, suppressed TGF-β transcriptional activation. Moreover, we show that TrkC directly binds to the TβRII, thereby preventing it from interacting with the type I TGF-β receptor (TβRI). These results indicate that TrkC is an inhibitor of TGF-β tumor suppressor activity.
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