Kitai Yuichi, Iwakami Masashi, Saitoh Kodai, Togi Sumihito, Isayama Serina, Sekine Yuichi, Muromoto Ryuta, Kashiwakura Jun-Ichi, Yoshimura Akihiko, Oritani Kenji, Matsuda Tadashi
From the Department of Immunology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Kita 12, Nishi 6, Kita-Ku, Sapporo, Hokkaido 060-0812.
the the Department of Microbiology and Immunology, Keio University School of Medicine, Tokyo 160-8582, and.
J Biol Chem. 2017 Nov 24;292(47):19392-19399. doi: 10.1074/jbc.M117.802884. Epub 2017 Oct 6.
Signal-transducing adaptor family member-2 (STAP-2) is an adaptor protein that regulates various intracellular signaling pathways and promotes tumorigenesis in melanoma and breast cancer cells. However, the contribution of STAP-2 to the behavior of other types of cancer cells is unclear. Here, we show that STAP-2 promotes tumorigenesis of prostate cancer cells through up-regulation of EGF receptor (EGFR) signaling. Tumor growth of a prostate cancer cell line, DU145, was strongly decreased by STAP-2 knockdown. EGF-induced gene expression and phosphorylation of AKT, ERK, and STAT3 were significantly decreased in STAP-2-knockdown DU145 cells. Mechanistically, we found that STAP-2 interacted with EGFR and enhanced its stability by inhibiting c-CBL-mediated EGFR ubiquitination. Our results indicate that STAP-2 promotes prostate cancer progression via facilitating EGFR activation.
信号转导衔接蛋白家族成员2（STAP-2）是一种衔接蛋白，可调节多种细胞内信号通路，并促进黑色素瘤和乳腺癌细胞的肿瘤发生。然而，STAP-2对其他类型癌细胞行为的作用尚不清楚。在此，我们表明STAP-2通过上调表皮生长因子受体（EGFR）信号促进前列腺癌细胞的肿瘤发生。STAP-2基因敲低后，前列腺癌细胞系DU145的肿瘤生长显著降低。在STAP-2基因敲低的DU145细胞中，表皮生长因子（EGF）诱导的AKT、ERK和STAT3的基因表达及磷酸化显著降低。机制上，我们发现STAP-2与EGFR相互作用，并通过抑制c-CBL介导的EGFR泛素化增强其稳定性。我们的结果表明，STAP-2通过促进EGFR激活促进前列腺癌进展。
