FOXD3 is a Tumor Suppressor of Colon Cancer by Inhibiting EGFR-Ras-Raf-MEK-ERK Signal Pathway

Overview

Journal Oncotarget

Specialty Oncology

Date 2016 Dec 8

PMID 27926503

Citations 23

Authors

Kun Li

Qunfeng Guo

Jun Yang

Hui Chen

Kewen Hu

Juan Zhao

Shunxin Zheng

Xiufeng Pang

Sufang Zhou

Yongyan Dang

Lei Li

Affiliations

Soon will be listed here.

Abstract

Forkhead box D3 (FOXD3), as a transcriptional repressor, is well known to be involved in the regulation of development. Although FoxD3 is associated with several cancers, its role in colon cancer and the underlying mechanism are still unclear. Here, we first showed that FOXD3 knockdown dramatically increased the proliferation of human colon cancer cells, enhanced cell invasive ability and inhibited cell apoptosis. In vivo xenograft studies confirmed that the FOXD3-knockdown cells were more tumorigenic than the controls. Silencing FOXD3 markedly activated EGFR/Ras/Raf/MEK/ERK pathway in human colon cancer cells. In addition, blocking EGFR effectively decreased the activity of MAPK induced by FOXD3 knockdown. In human cancer tissue, the expression of FOXD3 was reduced, however, the EGFR/Ras/Raf/MEK/ERK pathway was activated. Our study indicates that FOXD3 may play a protective role in human colon formation by regulating EGFR/Ras/Raf/MEK/ERK signal pathway. It is proposed that FOXD3 may have potential as a new therapeutic target in human colon cancer treatment.

Citing Articles

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