Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Sep 15, 2018; 10(9): 244-259
Published online Sep 15, 2018. doi: 10.4251/wjgo.v10.i9.244
Colorectal carcinogenesis: Insights into the cell death and signal transduction pathways: A review
Ashok kumar Pandurangan, Thomas Divya, Kalaivani Kumar, Vadivel Dineshbabu, Bakthavatchalam Velavan, Ganapasam Sudhandiran
Ashok kumar Pandurangan, Thomas Divya, Vadivel Dineshbabu, Bakthavatchalam Velavan, Ganapasam Sudhandiran, Cell Biology Laboratory, Department of Biochemistry, University of Madras, Guindy Campus, Chennai 600025, India
Ashok kumar Pandurangan, Kalaivani Kumar, School of Life sciences, B.S. Abdur Rahman Crescent Institute of Science and Technology, Chennai 600048, India
Author contributions: Pandurangan AK, Divya T, Kumar K, Dineshbabu V and Sudhandiran G wrote the manuscript; Divya T and Velavan B designed the figures and consolidated the references; Sudhandiran G analysed the data, selected the references and finalised the manuscript.
Conflict-of-interest statement: We, the authors declare no conflict of interest.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Correspondence to: Ganapasam Sudhandiran, MPhil, MSc, PhD, Associate Professor, Cell Biology Laboratory, Department of Biochemistry, University of Madras, Guindy Campus, Chennai 600025, India.
Telephone: +91-44-22202733
Received: April 16, 2018
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.

Keywords: Colorectal cancer, Cell death, Apoptosis, Autophagy, Inflammation, Hippo signalling, Nuclear factor erythroid 2-related factor 2, Wnt signaling

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.