Autocrine BMP-4 signaling promotes survival of colorectal cancer cells.. Homo sapiens

Prognoses are poor for colorectal cancer (CRC) patients with metastatic lesions, leading to high demand for the development of novel molecular target therapies. Here, we demonstrate that expression of bone morphogenetic protein 4 (BMP4) is universally up-regulated and endogenous BMP signaling is activated in human CRC cells and tissues. Inhibition of endogenous BMP signaling by the BMP type I receptor inhibitor LDN-193189 led to elevated expression of dual specificity phosphatase 5 (DUSP5) in CRC cells, inducing apoptosis through the dephosphorylation of Erk MAP kinase. Administration of LDN-193189 to mice diminished tumor formation of CRC cells in vivo. Our findings thus suggest that inhibition of autocrine BMP-4 by BMP inhibitors represents a promising candidate method for treatment of CRC. Overall design: Target genes for BMPs in CRC cells were identified using LDN-193189.