Trobridge P, Knoblaugh S, Washington MK, Munoz NM, Tsuchiya KD, Rojas A, Song X, Ulrich CM, Sasazuki T, Shirasawa S, Grady WM. TGF-beta receptor inactivation and mutant Kras induce intestinal neoplasms in mice via a beta-catenin-independent pathway. Gastroenterology. 2009 May;136(136). 1680-8.e7. PMID: 19208363 [PubMed] PMCID: PMC2782436 NIHMSID: NIHMS158103.
During colorectal cancer pathogenesis, mutations and epigenetic events cause neoplastic behavior in epithelial cells by deregulating the Wnt, Ras-Raf-extracellular signal-regulated kinase (ERK), and transforming growth factor (TGF)-beta-signaling pathways, among others. The TGF-beta-signaling pathway is often inactivated in colon cancer cells by mutations in the gene encoding the TGF-beta receptor TGFBR2. The RAS-RAF-ERK pathway is frequently up-regulated in colon cancer via mutational activation of KRAS or BRAF. We assessed how these pathways interact in vivo and affect formation of colorectal tumors.