Xiang Shihao, Wang Na, Hui Pingping, Ma Jiali
Department of Gastroenterology, Shanghai Tongren Hospital, Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Department of Gastroenterology, Shanghai Tongren Hospital, Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Biochem Biophys Res Commun. 2017 Mar 18;484(4):719-725. doi: 10.1016/j.bbrc.2017.01.095. Epub 2017 Jan 20.
Here, we focused on the potential function of Gab3, an uncommon Gab family protein, in human colorectal cancer (CRC) cells. We found that Gab3 was only expressed in human colon cancer tissues as well as in established (HCT-116 and HT-29 lines) and primary human CRC cells. It was however absent in normal human colon cancer tissues and in FHC colon epithelial cells. Knockdown of Gab3 by targeted-shRNAs inhibited proliferation of the CRC cells. Reversely, exogenous over-expression of Gab3 promoted CRC cell proliferation. At the signaling level, Gab3 co-precipitated with p85 and SHP2 in CRC cells, which was required for subsequent Akt and Erk activation. Gab3 shRNA knockdown inhibited Akt and Erk activation, yet Gab3 over-expression augmented it. In vivo, HCT-116 xenograft tumor growth in severe combined immune deficient (SCID) mice was suppressed following expressing Gab3 shRNAs. Meanwhile, Akt and Erk activation in Gab3 shRNA-expressing tumors was also largely inhibited. Together, our results suggest that Gab3 expression in CRC cells is important for Akt-Erk activation and cell proliferation.
在此，我们聚焦于Gab3（一种不常见的Gab家族蛋白）在人结肠直肠癌（CRC）细胞中的潜在功能。我们发现Gab3仅在人结肠癌组织以及已建立的（HCT - 116和HT - 29细胞系）和原代人CRC细胞中表达。然而，在正常人类结肠组织和FHC结肠上皮细胞中未检测到。通过靶向shRNA敲低Gab3可抑制CRC细胞的增殖。相反，外源性过表达Gab3可促进CRC细胞增殖。在信号传导水平上，Gab3在CRC细胞中与p85和SHP2共沉淀，这是随后Akt和Erk激活所必需的。Gab3 shRNA敲低抑制了Akt和Erk激活，但Gab3过表达增强了它们的激活。在体内，在严重联合免疫缺陷（SCID）小鼠中，表达Gab3 shRNAs后，HCT - 116异种移植肿瘤的生长受到抑制。同时，在表达Gab3 shRNA的肿瘤中，Akt和Erk激活也被大大抑制。总之，我们的结果表明，Gab3在CRC细胞中的表达对于Akt - Erk激活和细胞增殖很重要。
