Published online Sep 15, 2018. doi: 10.4251/wjgo.v10.i9.244
Peer-review started: April 16, 2018
First decision: April 27, 2018
Revised: June 5, 2018
Accepted: June 28, 2018
Article in press: June 28, 2018
Published online: September 15, 2018
Colorectal carcinogenesis (CRC) imposes a major health burden in developing countries. It is the third major cause of cancer deaths. Despite several treatment strategies, novel drugs are warranted to reduce the severity of this disease. Adenomatous polyps in the colon are the major culprits in CRC and found in 45% of cancers, especially in patients 60 years of age. Inflammatory polyps are currently gaining attention in CRC, and a growing body of evidence denotes the role of inflammation in CRC. Several experimental models are being employed to investigate CRC in animals, which include the APCmin/+ mouse model, Azoxymethane, Dimethyl hydrazine, and a combination of Dextran sodium sulphate and dimethyl hydrazine. During CRC progression, several signal transduction pathways are activated. Among the major signal transduction pathways are p53, Transforming growth factor beta, Wnt/β-catenin, Delta Notch, Hippo signalling, nuclear factor erythroid 2-related factor 2 and Kelch-like ECH-associated protein 1 pathways. These signalling pathways collaborate with cell death mechanisms, which include apoptosis, necroptosis and autophagy, to determine cell fate. Extensive research has been carried out in our laboratory to investigate these signal transduction and cell death mechanistic pathways in CRC. This review summarizes CRC pathogenesis and the related cell death and signal transduction pathways.
Core tip: Colorectal carcinogenesis (CRC) imposes a major health burden. This review addresses the cell death mechanisms and major signal transduction pathways involved in CRC. Regulated cell death is important for maintaining normal homeostasis, and the dysregulation of cell death processes leads to a spectrum of diseases including cancer. It is interesting to note that cell death pathways collaborate with each other, so understanding the various cell death mechanisms are therefore essential. CRC is orchestrated by various signal transduction pathways, which are used as drug targets. This review highlights the key concepts concerning cell death mechanisms and signal transduction in CRC.