STIP1 knockdown suppresses colorectal cancer cell proliferation, migration and invasion by inhibiting STAT3 pathway
STIP1 knockdown suppresses colorectal cancer cell proliferation, migration and invasion by inhibiting STAT3 pathway
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STIP1敲低通过抑制STAT3通路抑制结直肠癌细胞增殖、迁移和侵袭。
DOI：
10.1016/j.cbi.2021.109446
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发表时间：
2021-04-06
影响因子：
5.1
通讯作者：
He, YuLong
中科院分区：
文献类型：
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作者：
Xia, YuJian;Chen, Jian;He, YuLong
应激诱导磷酸化蛋白1 （STIP1）在肿瘤发生和发展中起重要作用。然而，STIP1在结直肠癌（CRC）中的作用尚不清楚。本研究旨在探讨STIP1在结直肠癌中的临床意义、生物学功能及潜在的分子机制。采用免疫组化（IHC）和Western bolt检测结直肠癌及邻近正常组织中STIP1蛋白水平。用shSTIP1处理DLD1和HCT116细胞系，用CCK8和菌落形成实验检测细胞增殖，用伤口愈合和transwell实验检测细胞迁移和侵袭。此外，我们还通过western blot和免疫荧光分析来探索STIP1在CRC进展中的潜在分子机制。我们发现STIP1在结直肠癌组织中的表达明显高于邻近正常组织。在结直肠癌患者中，高STIP1表达与较差的总生存期（OS）相关。此外，STIP1的分泌通过STAT3信号通路促进CRC细胞的增殖和侵袭，而STIP1的敲低则抑制CRC细胞的增殖、迁移和侵袭。在机制上，STIP1敲低抑制了CRC中STAT3信号通路的激活。综上所述，STIP1敲低可通过抑制STAT3信号的激活抑制CRC细胞的增殖、迁移和侵袭，STIP1是CRC治疗的潜在靶点。
Stress-induced phosphoprotein 1 (STIP1) plays an important role in cancer tumorigenesis and progression. However, the role of STIP1 in colorectal cancer (CRC) remains unclear. This study aimed to explore clinical significance, biological function and potential molecular mechanism of STIP1 in CRC. Immunohistochemistry (IHC) and Western bolt were performed to detect STIP1 protein level in CRC and adjacent normal tissues. DLD1 and HCT116 cell lines were treated with shSTIP1, cell proliferation was detected by CCK8 and colony formation assays, and cell migration and invasion were detected by wound healing and transwell assays. Moreover, western blot and immunofluorescence assays were performed to explore the potential molecular mechanism of STIP1 in the progression of CRC. We found that STIP1 expression in CRC tissues was significantly higher than in adjacent normal tissues. High STIP1 expression was associated with poor overall survival (OS) in CRC patients. Furthermore, secreted STIP1 promoted CRC cell proliferation and invasion through STAT3 signaling pathway, while STIP1 knockdown inhibited the proliferation, migration and invasion of CRC cells. Mechanistically, STIP1 knockdown suppressed the activation of STAT3 signaling pathway in CRC. In conclusion, STIP1 knockdown suppresses CRC cell proliferation, migration and invasion by inhibiting the activation of STAT3 signaling, and STIP1 is a potential target for CRC therapy.