title: SGT1 regulates Akt signaling by promoting beta-TrCP-dependent PHLPP1 degradation in gastric cancer cells.
abstract: SGT1 (suppressor of G2 allele of Skp1) plays a role in various cellular processes including kinetochore assembly and protein ubiquitination by interacting with Skp1, a component of SCF E3 ligase complex. However, the function of SGT1 in cancer is largely unknown. Here, we showed that SGT1 was over-expressed in gastric cancer tissues and silencing of SGT1 by siRNAs significantly inhibited the growth and colony formation of gastric cancer cells. We further showed that SGT1 could regulate Akt signaling pathway by modulating Akt ser473 phosphorylation status. Moreover, we found that SGT1 was able to regulate the stability of PHLPP1, which is the direct phosphatase for Akt ser473 phosphorylation. Immunoprecipitation assay revealed that SGT1 could enhance the binding between PHLPP1 and beta-TrCP which has been documented to be able to target PHLPP1 for destruction. Decreased PHLPP1 in SGT1 over-expressed gastric cancer cells failed to dephosphorylate Akt and resulted in increased Akt ser473 phosphorylation and amplified downstream Akt signaling. Thus, our data revealed a previously uncovered role of SGT1 in gastric cancer development, and suggested that SGT1 could be a promising anti-cancer target to against gastric cancer.
authors: Department of General Surgery, Central Hospital of Fengxian District, Shanghai, China.
authors: Ganglong
authors: G
authors: Gao
authors: Tao
authors: T
authors: Kun
authors: Youhua
authors: Y
authors: Sheng
authors: Min
authors: M
authors: Qian
authors: Fanzhi
authors: F
authors: Kong
authors: Xiaoguang
authors: X
authors: Liu
authors: Zhenfeng
authors: Z
authors: Yu
authors: Haiqin
authors: H
authors: Zhang
authors: Qiang
authors: Q
authors: Zhang
authors: Jianping
authors: J
authors: Gu
authors: Xueli
authors: X
authors: Zhang
mesh_terms: D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009687:Nuclear Proteins / Q000378:metabolism*; D051058:Oncogene Protein v-akt / Q000378:metabolism*; D010749:Phosphoprotein Phosphatases / Q000378:metabolism*; D010766:Phosphorylation; D011485:Protein Binding; D059748:Proteolysis; D034741:RNA, Small Interfering; D015398:Signal Transduction; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D044844:beta-Transducin Repeat-Containing Proteins / Q000378:metabolism*
chemical_list: D018797:Cell Cycle Proteins; D009687:Nuclear Proteins; D034741:RNA, Small Interfering; C490164:SUGT1 protein, human; D044844:beta-Transducin Repeat-Containing Proteins; D051058:Oncogene Protein v-akt; C400601:PHLPP1 protein, human; D010749:Phosphoprotein Phosphatases