It takes a village: microbiota, parainflammation, paligenosis and bystander effects in colorectal cancer initiation.

Autor:	Wang X; Nantong Institute of Genetics and Reproductive Medicine, Nantong Maternity and Child Healthcare Hospital, Nantong University, Nantong, Jiangsu 226018, China.; School of Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, China., Undi RB; Department of Radiation Oncology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA., Ali N; Department of Internal Medicine, Section of Digestive Diseases and Nutrition, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.; Stephenson Cancer Center, Universi ty of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA., Huycke MM; Department of Radiation Oncology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.; Stephenson Cancer Center, Universi ty of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
Jazyk:	angličtina
Zdroj:	Disease models & mechanisms [Dis Model Mech] 2021 May 01; Vol. 14 (5). Date of Electronic Publication: 2021 May 10.
DOI:	10.1242/dmm.048793
Abstrakt:	Sporadic colorectal cancer (CRC) is a leading cause of worldwide cancer mortality. It arises from a complex milieu of host and environmental factors, including genetic and epigenetic changes in colon epithelial cells that undergo mutation, selection, clonal expansion, and transformation. The gut microbiota has recently gained increasing recognition as an additional important factor contributing to CRC. Several gut bacteria are known to initiate CRC in animal models and have been associated with human CRC. In this Review, we discuss the factors that contribute to CRC and the role of the gut microbiota, focusing on a recently described mechanism for cancer initiation, the so-called microbiota-induced bystander effect (MIBE). In this cancer mechanism, microbiota-driven parainflammation is believed to act as a source of endogenous mutation, epigenetic change and induced pluripotency, leading to the cancerous transformation of colon epithelial cells. This theory links the gut microbiota to key risk factors and common histologic features of sporadic CRC. MIBE is analogous to the well-characterized radiation-induced bystander effect. Both phenomena drive DNA damage, chromosomal instability, stress response signaling, altered gene expression, epigenetic modification and cellular proliferation in bystander cells. Myeloid-derived cells are important effectors in both phenomena. A better understanding of the interactions between the gut microbiota and mucosal immune effector cells that generate bystander effects can potentially identify triggers for parainflammation, and gain new insights into CRC prevention. Competing Interests: Competing interests The authors declare no competing or financial interests. (© 2021. Published by The Company of Biologists Ltd.)
Databáze:	MEDLINE
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