icts those associated with the incidence of CRC. Mutations in components of the canonical Wnt pathway lead to a constitutively active beta-catenin, the core component of the pathway. Mutations in the Apc gene are associated with adenomatous polyposis, a form of colorectal cancer; loss-of-function mutations in Axin 1 and 2 have been detected in rare cases. Apc along with Axin1 and 2 are components of the 'degradation complex' which in the absence of the wnt signal, sequesters beta-catenin in the cytoplasm, leading to its phosphorylation, subsequent ubiquitination and degradation. Mutations in beta-catenin itself are clustered within an N-terminal region harboring the residues essential for its phosphorylation. In the altered TGF-beta Smad dependent signaling, the normal tumor suppressing function of the pathway is switched to a tumor stimulating one by mechanisms that are poorly understood. Mutations in ligand and receptors as well as in the Smad components of the pathway have been linked to colorectal and many other types of cancer. Altered DNA mismatch repair pathway (MMR) has long been identified as a primary cause of the hereditary colorectal cancer and it has also been shown to relate to a fraction of the sporadic form of the disease. Mutations have been found in the Msh2 and 6 homologs of E. coli MutS and the Mlh1, Pms1 and 2 homologs of E. coli MutL. The MMR pathway, conserved from bacterium to man, has been well characterized in E.coli and for eukaryotes, in S. cerevisiae. MutS is involved in the first step of mismatch recognition while MutL couples this event to next steps in the pathway. Other genes whose mutations have been implicated in CRC disease pathway (for some, with contradictory evidence) include Braf, the upper kinase tier of the Raf/Mek/Erk MAPK signaling pathway, Kras upstream of it (and of other pathways) and the p53 transcription factor. In addition, several miRNA have been reported to be aberrantly expressed; interestingly some of the donwregulated miRNAs are p53 targets. Colorectal cancer is one of several types of tumors for which platinum (Pt)-containing drugs such as cisplatin are used as chemotherapy agents. To see the ontology report for annotations, GViewer and download click here
To see the Disease Ontology report for genes that in some fashion have been associated with colorectal neoplasms or suspected to confer susceptibility, click here
To link to the Cancer Disease Portal, click here
[click to see the associated KEGG map - map005210]...(less)