Loss of Bcl-G, a Bcl-2 family member, augments the development of inflammation-associated colorectal cancer

• Published in: Cell death and differentiation Vol. 27; no. 2; pp. 742 - 757
• Main Authors: Nguyen, Paul M., Dagley, Laura F., Preaudet, Adele, Lam, Nga, Giam, Maybelline, Fung, Ka Yee, Aizel, Kaheina, van Duijneveldt, Gemma, Tan, Chin Wee, Hirokawa, Yumiko, Yip, Hon Yan K., Love, Christopher G., Poh, Ashleigh R., Cruz, Akshay D’, Burstroem, Charlotte, Feltham, Rebecca, Abdirahman, Suad M., Meiselbach, Kristy, Low, Ronnie Ren Jie, Palmieri, Michelle, Ernst, Matthias, Webb, Andrew I., Burgess, Tony, Sieber, Oliver M., Bouillet, Philippe, Putoczki, Tracy L.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.02.2020; Nature Publishing Group
• Subjects: 13/106; 13/2; 13/51; 14/63; 38/39; 38/90; 631/67/1244; 631/67/70; 64/60; 96/31; Animals; Apoptosis; Bcl-2 protein; Biochemistry; Biomedical and Life Sciences; Cancer; Cell Biology; Cell Cycle Analysis; Colitis; Colitis - metabolism; Colitis - pathology; Colon; Colon cancer; Colorectal cancer; Colorectal carcinoma; Colorectal Neoplasms - metabolism; Colorectal Neoplasms - pathology; Embryogenesis; Epithelial cells; Homeostasis; Humans; Immune system; Inflammation; Inflammation - metabolism; Inflammation - pathology; Life Sciences; Mice; Mice, Knockout; Mucin; Proteomics; Proto-Oncogene Proteins c-bcl-2 - deficiency; Proto-Oncogene Proteins c-bcl-2 - genetics; Proto-Oncogene Proteins c-bcl-2 - metabolism; Stem Cells; Tumorigenesis
• ISSN: 1350-9047; 1476-5403
• DOI: 10.1038/s41418-019-0383-9

Gastrointestinal epithelial cells provide a selective barrier that segregates the host immune system from luminal microorganisms, thereby contributing directly to the regulation of homeostasis. We have shown that from early embryonic development Bcl-G, a Bcl-2 protein family member with unknown function, was highly expressed in gastrointestinal epithelial cells. While Bcl-G was dispensable for normal growth and development in mice, the loss of Bcl-G resulted in accelerated progression of colitis-associated cancer. A label-free quantitative proteomics approach revealed that Bcl-G may contribute to the stability of a mucin network, which when disrupted, is linked to colon tumorigenesis. Consistent with this, we observed a significant reduction in Bcl-G expression in human colorectal tumors. Our study identifies an unappreciated role for Bcl-G in colon cancer.