Oncotarget

Research Papers:

C-kit signaling promotes proliferation and invasion of colorectal mucinous adenocarcinoma in a murine model

Jun Tan, Shu Yang, Ping Shen, Haimei Sun, Jie Xiao, Yaxi Wang, Bo Wu, Fengqing Ji, Jihong Yan, Hong Xue and Deshan Zhou _

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Oncotarget. 2015; 6:27037-27048. https://doi.org/10.18632/oncotarget.4815

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Abstract

Jun Tan1,2, Shu Yang1,2,3, Ping Shen1,3, Haimei Sun1,2,3, Jie Xiao1,3, Yaxi Wang1,2, Bo Wu1,2,3, Fengqing Ji1,2,3, Jihong Yan1, Hong Xue1, Deshan Zhou1,2,3

1Department of Histology and Embryology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, P. R. China

2Beijing Key Laboratory of Cancer Invasion and Metastasis Research, Beijing 100069, P. R. China

3Cancer Institute of Capital Medical University, Beijing 100069, P. R. China

Correspondence to:

Deshan Zhou, e-mail: zhoudeshan2008@163.com

Keywords: colorectal mucinous adenocarcinoma, C-kit, ETV4, murine model

Received: March 24, 2015     Accepted: August 20, 2015     Published: September 02, 2015

ABSTRACT

It was reported that the receptor tyrosine kinase (RTK) family often highly expressed in several mucinous carcinomas. In the present study, we established a murine model of colorectal mucinous adenocardinoma (CRMAC) by treating C57 mice [both wild type (WT) and loss-of-function c-kit mutant type (Wads−/−)] with AOM+DSS for 37 weeks and found that c-kit, a member of RTK family, clearly enhanced the tumor cell proliferation by decreasing p53 and increasing cyclin D1 through AKT pathway. Significantly, c-kit strongly promoted tumor cell invasiveness by increasing ETV4, which induced MMP7 expression and epithelial-mesenchymal transition (EMT) via ERK pathway. In vitro up- or down-regulating c-kit activation in human colorectal cancer HCT-116 cells further consolidated these results. In conclusion, our data suggested that the c-kit signaling obviously promoted proliferation and invasion of CRMAC. Therefore, targeting the c-kit signaling and its downstream molecules might provide the potential strategies for treatment of patients suffering from CRMAC in the future.


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