Department of Gastroenterology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, P.R. China.
Department of Gastroenterology, Ruian People's Hospital, Wenzhou, Zhejiang 325200, P.R. China.
Mol Med Rep. 2018 Mar;17(3):3797-3806. doi: 10.3892/mmr.2017.8283. Epub 2017 Dec 15.
Rab11-family interacting proteins (Rab11‑FIPs) are associated with the progression of various tumors; however, their expression and clinical significance in colorectal cancer (CRC) remains largely undetermined. In this study, the clinical implications, functions and underlying mechanisms of Rab11‑FIP4 in CRC were investigated. Immunohistochemical analysis revealed that expression of Rab11‑FIP4 was significantly increased in human CRC tissues and correlated with poor prognosis of patients with CRC. Overexpression of Rab11‑FIP4 in the CRC cell line significantly promoted cell proliferation, migration and invasion in vitro and tumor metastasis in vivo. Furthermore, the results of a co‑immunoprecipitation assay and western blot analysis demonstrated that Rab11‑FIP4 interacted with Rab11 and insulin‑like growth factor 1 receptor, and increased the phosphorylation of extracellular signal‑regulated kinase 1/2 and AKT serine/threonine kinase. In addition, hypoxia contributed to the upregulation of Rab11‑FIP4 expression via hypoxia‑inducible factor‑1α activation of the Rab11‑FIP4 promoter. In conclusion, the results of the present study suggest that Rab11‑FIP4 may act as an oncogene in CRC, and may be a potential therapeutic target for the treatment of patients with CRC.
Rab11 家族相互作用蛋白(Rab11-FIPs)与多种肿瘤的进展相关;然而,其在结直肠癌(CRC)中的表达和临床意义在很大程度上仍未确定。在本研究中,研究了 Rab11-FIP4 在 CRC 中的临床意义、功能和潜在机制。免疫组织化学分析显示,Rab11-FIP4 在人 CRC 组织中的表达显著增加,并与 CRC 患者的预后不良相关。在 CRC 细胞系中过表达 Rab11-FIP4 显著促进了细胞在体外的增殖、迁移和侵袭以及体内的肿瘤转移。此外,免疫共沉淀测定和 Western blot 分析的结果表明,Rab11-FIP4 与 Rab11 和胰岛素样生长因子 1 受体相互作用,并增加了细胞外信号调节激酶 1/2 和 AKT 丝氨酸/苏氨酸激酶的磷酸化。此外,缺氧通过缺氧诱导因子-1α 激活 Rab11-FIP4 启动子促进 Rab11-FIP4 的表达上调。综上所述,本研究结果表明,Rab11-FIP4 可能在 CRC 中作为癌基因发挥作用,并且可能是治疗 CRC 患者的潜在治疗靶点。