Department of Gastrointestinal Surgery, The First Affiliated Hospital, Sun Yat-sen University, 58 Zhongshan 2nd Road, Guangzhou, Guangdong, 510080, China.
Department of Gastrointestinal Surgery, Seventh Affiliated Hospital of Sun Yat-sen University, No. 628, Shenyuan Road, Shenzhen, Guangdong, 518106, China.
Chem Biol Interact. 2021 May 25;341:109446. doi: 10.1016/j.cbi.2021.109446. Epub 2021 Mar 23.
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.
应激诱导磷蛋白 1（STIP1）在癌症的发生和发展中起着重要作用。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 CRC 中的临床意义、生物学功能和潜在的分子机制。免疫组织化学（IHC）和 Western blot 检测 CRC 及相邻正常组织中 STIP1 蛋白水平。用 shSTIP1 处理 DLD1 和 HCT116 细胞系，通过 CCK8 和集落形成实验检测细胞增殖，通过划痕愈合和 Transwell 实验检测细胞迁移和侵袭。此外，通过 Western blot 和免疫荧光实验探讨 STIP1 在 CRC 进展中的潜在分子机制。我们发现 CRC 组织中 STIP1 的表达明显高于相邻正常组织。高 STIP1 表达与 CRC 患者的总生存（OS）不良相关。此外，分泌的 STIP1 通过 STAT3 信号通路促进 CRC 细胞增殖和侵袭，而 STIP1 敲低抑制 CRC 细胞的增殖、迁移和侵袭。机制上，STIP1 敲低抑制了 CRC 细胞中 STAT3 信号通路的激活。总之，STIP1 敲低通过抑制 STAT3 信号通路的激活抑制 CRC 细胞的增殖、迁移和侵袭，STIP1 是 CRC 治疗的潜在靶点。
