RRC ID 52291
著者 Qin H, Rasul A, Li X, Masood M, Yang G, Wang N, Wei W, He X, Watanabe N, Li J, Li X.
タイトル CD147-induced cell proliferation is associated with Smad4 signal inhibition.
ジャーナル Exp Cell Res
Abstract CD147 is a multifunctional trans-membrane glycoprotein, which is highly expressed in many cancers. However, the mechanism by which CD147 modulates cell proliferation is not fully understood. The aim of this study is to investigate the role of CD147 in cell proliferation associated with the TGF-β/Smad4 signaling pathway. Here, we used cell viability and clone formation assays in LNCaP prostate cancer cells to demonstrate that CD147 promotes cell proliferation. The luciferase assay and western blotting show that silencing CD147 using shRNA enhances transcription and expression of p21WAF1. Using immunofluorescence and nuclear-cytoplasmic separation, we show that this is primarily attributed to transport of Smad4 from the cytoplasm to nucleus. Other assays (GST pull-down, co-immunoprecipitation and immunofluorescence) demonstrate that Smad4 is a new interaction partner of CD147, with the Smad4 MH2 domain and CD147 intracellular domain (CD147-ICD) being involved in the interaction. Furthermore, we report that a phosphoserine (pSer) in CD147 (pSer252) is responsible for this interaction and inhibition of the Smad4/p21WAF1 signal that promotes cell proliferation. Our results provide a novel molecular mechanism for CD147-induced cell proliferation associated with Smad4 signal inhibition.
巻・号 358(2)
ページ 279-289
公開日 2017-9-15
DOI 10.1016/j.yexcr.2017.07.003
PII S0014-4827(17)30355-5
PMID 28684116
MeSH Basigin / genetics* Basigin / metabolism Cell Line, Tumor Cell Nucleus / metabolism Cell Proliferation / genetics* Cytoplasm / metabolism Humans Promoter Regions, Genetic / genetics* Signal Transduction / genetics* Smad4 Protein / metabolism* Trans-Activators / metabolism Transforming Growth Factor beta / metabolism
IF 3.383
引用数 5
リソース情報
ヒト・動物細胞 LNCap.FGC(RCB2144)