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

作者:Yokoyama Yuichiro; Watanabe Toshiaki; Tamura Yusuke; Hashizume Yoshinobu; Miyazono Kohei; Ehata Shogo
来源:Cancer Research, 2017, 77(15): 4026-4038.
DOI:10.1158/0008-5472.CAN-17-0112

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.

  • 出版日期2017-8-1