Bone morphogenetic protein and activin signaling in colorectal cancer

The roles in colon cancer pathogenesis of the transforming growth factor family members bone morphogenetic protein (BMP) and activin have only recently been studied but are increasingly recognized as key. Like their more heavily investigated relative, transforming growth factor β, both BMP and activin are growth-suppressive in normal colonocytes, and their canonical intracellular SMAD signaling is disrupted to abate this suppression. For BMP, there is evidence that non-SMAD signaling pathways may mediate cell proliferation and contribute to the metastatic behavior of colon cancer. BMP signaling in particular is disrupted in the germline of patients with familial juvenile polyposis, an autosomal dominant syndrome with a 12-fold increase in risk for colon cancer over the general population. Researchers are actively investigating cellular and signaling mechanisms by which BMP and activin may initiate and drive proliferation and allow cells to exhibit metastatic properties.