Autocrine BMP-4 signaling is a therapeutic target in colorectal cancer

Poor prognoses for colorectal cancer (CRC) 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 CRC 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 CRC cells, inducing apoptosis via dephosphorylation of Erk MAPK. Administering LDN-193189 to mice diminished tumor formation of CRC cells. Our findings suggest inhibition of autocrine BMP-4 as a candidate treatment strategy for CRC.

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