Molecular and cellular pathways in colorectal cancer: apoptosis, autophagy and inflammation as key players

Abstract

Background

Colorectal carcinogenesis (CRC) is one of the most aggressive forms of cancer, particularly in developing countries. It accounts for the second and third-highest reason for cancer-induced lethality in women and men respectively. CRC involves genetic and epigenetic modifications in colonic epithelium, leading to colon adenocarcinoma. The current review highlights the pathogenic mechanisms and multifactorial etiology of CRC, influenced by apoptosis, inflammation, and autophagy pathways.

Methods

We have carried out a selective literature review on mechanisms contributing to the pathogenesis of CRC.

Results

Resistance to senescence and apoptosis of the mesenchymal cells, which play a key role in intestinal organogenesis, morphogenesis and homeostasis, appears important for sporadic CRC. Additionally, inflammation-associated tumorigenesis is a key incident in CRC, supported by immune disruptors, adaptive and innate immune traits, environmental factors, etc. involving oxidative stress, DNA damage and epigenetic modulations. The self-digesting mechanism, autophagy, also plays a twin role in CRC through the participation of LC3/LC3-II, Beclin-1, ATG5, other autophagy proteins, and Inflammatory Bowel Disease (IBD) susceptibility genes. It facilitates the promotion of effective surveillance pathways and stimulates the generation of malignant tumor cells. The autophagy and apoptotic pathways undergo synergistic or antagonistic interactions in CRC and bear a critical association with IBD that results from the pro-neoplastic effects of persistent intestinal inflammation. Conversely, pro-inflammatory factors stimulate tumor growth and angiogenesis and inhibit apoptosis, suppressing anti-tumor activities.

Conclusion

Hence, research attempts for the development of potential therapies for CRC are in progress, primarily based on combinatorial approaches targeting apoptosis, inflammation, and autophagy.

Keywords:

• Tumor growth
• colon
• adenomatous polyp
• caspase
• cytokine
• LC3

Author contribution

Dr Lei Yu and Dr Miao-Miao Zhang have written the Apoptosis and Autophagy concepts, respectively. Dr Ji-Guang Hou has written the Inflammation concept and compiled the overall manuscript.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This research was supported by Health Talent Project of Jilin Provincial Department of Finance [2020SCZT066].