title: Colorectal cancer: role of commensal bacteria and bystander effects.
abstract: For years the human microbiota has been implicated in the etiology of colorectal cancer (CRC). However, identifying the molecular mechanisms for how aneuploidy and chromosomal instability (CIN) arise in sporadic and colitis-associated CRC has been difficult. In this Addendum we review recent work from our laboratory that explore mechanisms by which intestinal commensals polarize colon macrophages to an M1 phenotype to generate a bystander effect (BSE) that leads to mutations, spindle malfunction, cell cycle arrest, tetraploidy, and aneuploidy in epithelial cells. BSE represents the application of a phenomenon initially described in the radiation biology field. The result of commensal-driven BSE on colon epithelial cells is aneuploidy, chromosomal instability (CIN), expression of stem cell and tumor stem cell markers and, ultimately, malignant transformation. Our findings provide a conceptual framework for integrating the microbiota with aging, cyclooxygenase (COX)-2, and inflammation as risk factors for CRC.
authors.affiliation: a Department of Radiation Oncology ; University of Oklahoma Health Sciences Center ; Oklahoma City , OK USA.
authors.forename: Xingmin
authors.initials: X
authors.lastname: Wang
authors.affiliation: b Department of Medicine ; University of Oklahoma Health Sciences Center ; Oklahoma City , OK USA.|c The Muchmore Laboratories for Infectious Diseases Research; Oklahoma City VA Health Care System ; Oklahoma City , OK USA.
authors.forename: Mark M
authors.initials: MM
authors.lastname: Huycke
mesh_terms: D000782:Aneuploidy; D000818:Animals; D024201:Bystander Effect; D002471:Cell Transformation, Neoplastic; D015179:Colorectal Neoplasms / Q000235:genetics / Q000382:microbiology*; D004249:DNA Damage; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism / Q000382:microbiology; D064307:Microbiota; D013559:Symbiosis
keywords: Bystander effects; carcinogenesis; colorectal cancer; commensal bacteria