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Cancer Res. 2017 Aug 1;77(15):4026-4038. doi: 10.1158/0008-5472.CAN-17-0112. Epub 2017 Jun 13.

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

Author information

1
Department of Molecular Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
2
Department of Surgical Oncology, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
3
RIKEN Program for Drug Discovery and Medical Technology Platforms, Wako, Saitama, Japan.
4
Department of Molecular Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. ehata-jun@umin.ac.jp miyazono@m.u-tokyo.ac.jp.

Abstract

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. Cancer Res; 77(15); 4026-38. ©2017 AACR.

PMID:
28611046
DOI:
10.1158/0008-5472.CAN-17-0112
[Indexed for MEDLINE]
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