Cortactin contributes to the tumorigenicity of colorectal cancer by promoting cell proliferation

Wu,Huo; Cheng,Xi; Ji,Xiaopin; He,Yonggang; Jing,Xiaoqian; Wu,Haoxuan; Zhao,Ren

doi:10.3892/or.2016.5207

Cortactin contributes to the tumorigenicity of colorectal cancer by promoting cell proliferation

Authors:
- Huo Wu
- Xi Cheng
- Xiaopin Ji
- Yonggang He
- Xiaoqian Jing
- Haoxuan Wu
- Ren Zhao
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Affiliations: Department of General Surgery, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, P.R. China
Published online on: October 27, 2016 https://doi.org/10.3892/or.2016.5207
Pages: 3497-3503

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Abstract

Cortactin is a scaffolding protein that regulates Arp2/3-mediated actin polymerization. We showed in a previous study that cortactin was highly expressed in human stage II-III colorectal cancer (CRC) tissues. In the present study, using colony formation and CCK-8 assays, we showed that overexpression of cortactin accelerated the proliferation of CRC cells. Flow cytometric assays revealed that cortactin promoted G1/S phase cell cycle transition. Later, we constructed the phosphorylation mutation of cortactin at the Tyr421 residue. Colony formation and CCK-8 assays showed that cortactin/Tyr421A lost its ability to promote cell proliferation. Western blot analysis indicated that cortactin activated cyclin D1, but not cortactin/Tyr421A. Further study in nude mice revealed that there was a greater decrease in both tumor volume and tumor weight in animals injected with SW480/cortactin/Tyr421A cells than in those injected with SW480/cortactin/WT cells. Thus, the present study demonstrates that the cortactin Tyr421 residue is required to promote cell proliferation both in vitro and in vivo.

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