信号转导和转录激活蛋白2（STAP-2）通过增强表皮生长因子受体的稳定性来促进前列腺癌生长。
STAP-2 protein promotes prostate cancer growth by enhancing epidermal growth factor receptor stabilization.
作者信息
Kitai Yuichi, Iwakami Masashi, Saitoh Kodai, Togi Sumihito, Isayama Serina, Sekine Yuichi, Muromoto Ryuta, Kashiwakura Jun-Ichi, Yoshimura Akihiko, Oritani Kenji, Matsuda Tadashi
机构信息
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.
出版信息
J Biol Chem. 2017 Nov 24;292(47):19392-19399. doi: 10.1074/jbc.M117.802884. Epub 2017 Oct 6.
Abstract
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.
摘要
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。
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STAP-2 Protein Expression in B16F10 Melanoma Cells Positively Regulates Protein Levels of Tyrosinase, Which Determines Organs to Infiltrate in the Body.STAP-2蛋白在B16F10黑色素瘤细胞中的表达正向调节酪氨酸酶的蛋白水平，而酪氨酸酶决定了体内浸润的器官。
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STAP-2 interacts with and modulates BCR-ABL-mediated tumorigenesis.STAP-2 与 BCR-ABL 介导的肿瘤发生相互作用并调节其活性。
Oncogene. 2012 Oct 4;31(40):4384-96. doi: 10.1038/onc.2011.604. Epub 2012 Jan 9.
9
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10
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