Hypoxia-induced Rab11-family interacting protein 4 expression promotes migration and invasion of colon cancer and correlates with poor prognosis

Wang,Jian‑Zhang; Yang,Shou‑Xing; Ye,Fangpeng; Xia,Xuan‑Ping; Shao,Xiao‑Xiao; Xia,Sheng‑Long; Zheng,Bo; Xu,Chang‑Long

doi:10.3892/mmr.2017.8283

Hypoxia-induced Rab11-family interacting protein 4 expression promotes migration and invasion of colon cancer and correlates with poor prognosis

Authors:
- Jian‑Zhang Wang
- Shou‑Xing Yang
- Fangpeng Ye
- Xuan‑Ping Xia
- Xiao‑Xiao Shao
- Sheng‑Long Xia
- Bo Zheng
- Chang‑Long Xu
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Affiliations: 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
Published online on: December 15, 2017 https://doi.org/10.3892/mmr.2017.8283
Pages: 3797-3806

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Abstract

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.

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