%0 Journal Article
%T Overexpression of MACC1 leads to downstream activation of HGF/MET and potentiates metastasis and recurrence of colorectal cancer
%A Lisa A Boardman
%J Genome Medicine
%D 2009
%I BioMed Central
%R 10.1186/gm36
%X To date, the most reliable prognostic indicator for colorectal cancer (CRC) has been stage, but discerning which of those patients with stage II or III disease will be among the 25-51% of cases to develop recurrent cancer and succumb to the disease remains one of the most problematic and frustrating issues concerning clinical care and cancer surveillance strategies for CRC patients. Recent guidelines by the European Group of Tumor Markers for the clinical use of CRC markers determined that currently only measurement of serum carcinoembryonic antigen (CEA) every two to three months may be of value for recognizing recurrence in patients with stage II or III disease [1]. Other serum markers, including cancer antigen CA19.9, CA242 and tissue inhibitor of metalloproteinases (TIMP-1), or the tumor markers thymidylate synthase, microsatellite instability, p53, K-ras, and deleted in colon cancer (DCC) offer no advantage beyond the limited specificity and sensitivity of CEA for early detection of cancer recurrence [1]. Stein et al. [2] report the association of overexpression of MACC1 with an increased risk for CRC metastasis, providing compelling data that this gene may be useful both as a prognostic marker and possibly as a chemopreventive or therapeutic target.MACC1 is located on chromosome 7p21.1 and regulates injury response and tissue growth via the HGF/MET signaling pathway. Of note, HGF and MET also map to chromosome 7 (7q21.1 and 7q31, respectively). Polysomy of chromosome 7 is a common finding in both glioblastomas and CRC tumors [3], and recent genome-wide analysis of siblings with familial CRC not related to known genetic conditions implicated 7q31 as a region linked to hereditary CRC [4].HGF regulates growth of liver sinusoidal endothelial cells and interacts with interleukin 7 to regulate the immune response to mucosal lymphocytes in the intestinal mucosa [5], mainly via activity in the stroma. The malaria parasite Plasmodium sporozoite stimulates stromal cell
%U http://genomemedicine.com/content/1/4/36