Figure 2.
Widespread extracellular matrix (ECM) pathway silencing by DNA hypermethylation in colon cancer. (A) Hypermethylated genes in colon cancer (green circled) are highlighted on a map of the ECM pathway. The network shows interaction of the genes with each other within the extracellular matrix. Circled (green) genes include 13 hypermethylated genes in CRC derived from our gene discovery approach (LAMA1, MMP2, FBN2, CPAMD8, NTNG1, NRCAM, EVL and GPNMB, FLNC, CD109, ICAM5, HAPLN1, and IGFBP3). Arrows indicate incoming (←) or outcomming (→) connector between proteins. Colors (Green/Red/Black) of line describe positive, negative, and unspecified effect of functional interaction (www.genego.com). An additional 6 genes including TIMP2, TIMP3, MMP9, Nidogen, Osteonectin, and PLAU were previously identified to be down-regulated in association with DNA methylation in other cancer types, and now are shown to be similarly altered in colon cancers in the present study. The functional gene ontology analysis was performed using the MetaCore database (GeneGo). The Table below the schematic figure shows the putative role of all of these 19 genes in the ECM pathway.