Autocrine BMP-4 Signaling Is a Therapeutic Target in Colorectal Cancer

被引：66

作者：

Yokoyama, Yuichiro ^{[1
,2
]}

Watanabe, Toshiaki ^{[2
]}

Tamura, Yusuke ^{[1
]}

Hashizume, Yoshinobu ^{[3
]}

Miyazono, Kohei ^{[1
]}

Ehata, Shogo ^{[1
]}

机构：

[1] Univ Tokyo, Grad Sch Med, Dept Mol Pathol, Tokyo, Japan

[2] Univ Tokyo, Dept Surg Oncol, Bunkyo Ku, Tokyo, Japan

[3] RIKEN, Program Drug Discovery & Med Technol Platforms, Wako, Saitama, Japan

来源：

CANCER RESEARCH | 2017年 / 77卷 / 15期

基金：

日本学术振兴会;

关键词：

SPECIFICITY PHOSPHATASE 5; BONE MORPHOGENETIC PROTEIN-2; GROWTH-FACTOR-BETA; TGF-BETA; DOWN-REGULATION; METASTASIS; INHIBITION; ACTIVATION; PATHWAY; ROLES;

D O I：

10.1158/0008-5472.CAN-17-0112

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Poor prognoses for colorectal cancer patients with metastatic lesions have driven demand for the development of novel targeted therapies. Here, we demonstrate that expression of bone morphogenetic protein 4 (BMP-4) is universally upregulated in human colorectal cancer cells and tissues, resulting in activated BMP signaling. Inhibition of endogenous BMP signaling by the BMP type I receptor inhibitor LDN-193189 elevated expression of the phosphatase DUSP5 in colorectal cancer cells, inducing apoptosis via dephosphorylation of Erk MAPK. Administering LDN-193189 to mice diminished tumor formation of colorectal cancer cells. Our findings suggest inhibition of autocrine BMP-4 as a candidate treatment strategy for colorectal cancer. (C) 2017 AACR.

引用

收藏

页码：4026 / 4038

页数：13

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