Bone morphogenetic protein and activin signaling in colorectal cancer

Abstract

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 , 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.

Genetics and Genetic Biomarkers in Sporadic Colorectal Cancer

“…SMAD4, SMAD2, ACVR2 , etc.) are commonly involved in sporadic CRCs [7,12–14,44,47,48]. As one-third of all CRC has a familial component but only a small portion of genetic causes overall identified, these human conditions should continue to provide information that may apply to sporadic CRC and its pathogenesis, with some as potential biomarkers for use for precision medicine.…”

Loss of SMAD4 From Colorectal Cancer Cells Promotes CCL15 Expression to Recruit CCR1+ Myeloid Cells and Facilitate Liver Metastasis

“…Not only TGF-β, but also BMP and activin signaling appears to be involved in the progression of CRC. 25 Thus, we investigated which particular signaling played major roles in CCL15 regulation. First, we determined the endogenous expression levels of TGF-β superfamily ligands in CRC cell lines, and found TGF-β1 and BMP4 at significant levels ( Supplementary Fig.…”

GRG Profiles: John M. Carethers

“…Barbara Jung, a talented physician-scientist in the laboratory at the time and currently the Gastroenterology Division Chief at the University of Illinois, Chicago, demonstrated the importance of the activin type 2 receptor, ACVR2, in colorectal cancer, both clinically and mechanistically [15, 16]. Stayce Beck, who received her PhD in my laboratory, was the first to show the importance of BMP in sporadic colorectal cancer behavior [17, 18]. Other talented post-docs working in this area were Sherry Huang, who focused on TGFβ in familial hamartomatous syndromes, and Jimmy Chow, who studied TGFβ signaling in pancreatic cancer.…”