Function and mode of action of cytohesins in the epidermal growth factor pathway in colorectal cancer cells

Pan,Tao; Sun,Junfeng; Zhou,Jun; Fu,Zhixuan; Hu,Yiwang; Zheng,Shu; Zhang,Suzhan

doi:10.3892/ol.2012.1064

Function and mode of action of cytohesins in the epidermal growth factor pathway in colorectal cancer cells

Authors:
- Tao Pan
- Junfeng Sun
- Jun Zhou
- Zhixuan Fu
- Yiwang Hu
- Shu Zheng
- Suzhan Zhang
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Affiliations: Cancer Institute, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009, P.R. China
Published online on: December 5, 2012 https://doi.org/10.3892/ol.2012.1064
Pages: 521-526

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Abstract

Cytohesins have been identified as cytoplasmic ErbB receptor activators in certain cancers, exhibiting an important role in ErbB signaling. However, whether cytohesins are essential in colorectal cancer is unknown. The aim of the present study was to investigate whether cytohesins contribute to the epidermal growth factor (EGF) pathway in colorectal cancer cells. RT‑PCR and immunofluorescence experiments were employed to detect the expression of cytohesins in colorectal cancer cell lines. The EGF pathway activation conditions were investigated by examining the phosphorylation of the epidermal growth factor receptor (EGFR) and intracellular signal-related kinases, with or without chemical inhibition (SecinH3) and knockdown of cytohesins. An MTT assay was conducted to examine the inhibitory effect of SecinH3 and cytohesin‑specific siRNA in HT‑29 cells. Results demonstrated that the four homologous members of the cytohesin family were expressed in the four colorectal cancer cell lines. Notably, a significantly higher expression level of cytohesin‑2 (ARNO) compared with the other three homologous family members was observed. Stimulation with EGF and SecinH3, as well as knockdown of ARNO, are capable of reducing EGF pathway activation and proliferation of HT‑29 cells. In conclusion, cytohesins play an essential role in the activation of the EGF pathway and may be a potential target in colorectal cancer therapy.

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