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假磷酸酶 STYX 通过抑制结直肠癌中 FBXW7 的功能促进肿瘤生长和转移。

Pseudophosphatase STYX promotes tumor growth and metastasis by inhibiting FBXW7 function in colorectal cancer.

机构信息

Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China; Institute of Digestive Surgery, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China.

Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China.

出版信息

Cancer Lett. 2019 Jul 10;454:53-65. doi: 10.1016/j.canlet.2019.04.014. Epub 2019 Apr 11.

Abstract

Serine/threonine/tyrosine interacting protein (STYX), a member of protein tyrosine phosphatases, has recently been reported as a potential oncogene. However, the role of STYX in colorectal cancer (CRC) remains unknown. In this study, we found that STYX was highly expressed in CRC tissues and closely correlated with tumor development and survival of CRC patients. In vitro studies showed that overexpression of STYX promoted proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) and inhibited apoptosis in CRC cells, while STYX knockdown had the opposite effects. Consistently, in vivo experiments showed that overexpression of STYX promoted tumor growth and lung metastasis. Mechanically, STYX bound to the F-box and WD repeat domain-containing7 (FBXW7) protein and inhibited its function. Co-regulation of STYX and FBXW7 expression reversed the biological changes mediated by regulation of STYX expression alone in CRC cells. Additionally, FBXW7 expression was negatively associated with STYX expression in CRC tissues, and low STYX levels accompanying high FBXW7 levels predicted favorable prognosis of CRC patients. In conclusion, our results suggest that STYX plays an oncogenic role by inhibiting FBXW7 and represents a potential therapeutic target and prognostic biomarker in CRC.

摘要

丝氨酸/苏氨酸/酪氨酸相互作用蛋白(STYX)是蛋白酪氨酸磷酸酶家族的一员,最近被报道为一种潜在的癌基因。然而,STYX 在结直肠癌(CRC)中的作用尚不清楚。在这项研究中,我们发现 STYX 在 CRC 组织中高度表达,与 CRC 患者的肿瘤发展和生存密切相关。体外研究表明,STYX 的过表达促进了 CRC 细胞的增殖、迁移、侵袭和上皮-间充质转化(EMT),并抑制了细胞凋亡,而 STYX 的敲低则产生了相反的效果。一致地,体内实验表明,STYX 的过表达促进了肿瘤生长和肺转移。在机制上,STYX 与 F-box 和 WD 重复结构域蛋白 7(FBXW7)蛋白结合并抑制其功能。STYX 和 FBXW7 表达的共同调节逆转了单独调节 STYX 表达在 CRC 细胞中介导的生物学变化。此外,CRC 组织中 FBXW7 的表达与 STYX 的表达呈负相关,而 STYX 水平低伴随 FBXW7 水平高预示着 CRC 患者的预后良好。总之,我们的研究结果表明,STYX 通过抑制 FBXW7 发挥致癌作用,代表了 CRC 潜在的治疗靶点和预后生物标志物。

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