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

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 func...

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Published inCell 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
LanguageEnglish
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
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Abstract 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.
AbstractList 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.
Author Poh, Ashleigh R.
Webb, Andrew I.
Giam, Maybelline
Love, Christopher G.
Meiselbach, Kristy
Preaudet, Adele
Dagley, Laura F.
Burgess, Tony
Feltham, Rebecca
Yip, Hon Yan K.
Sieber, Oliver M.
Nguyen, Paul M.
Aizel, Kaheina
Bouillet, Philippe
Fung, Ka Yee
Burstroem, Charlotte
Cruz, Akshay D
Lam, Nga
Putoczki, Tracy L.
Palmieri, Michelle
Ernst, Matthias
van Duijneveldt, Gemma
Tan, Chin Wee
Abdirahman, Suad M.
Low, Ronnie Ren Jie
Hirokawa, Yumiko
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PublicationTitle Cell death and differentiation
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  publication-title: Nat Rev Microbiol
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    fullname: MA McGuckin
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  publication-title: J Proteome Res
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Snippet Gastrointestinal epithelial cells provide a selective barrier that segregates the host immune system from luminal microorganisms, thereby contributing directly...
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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
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Title Loss of Bcl-G, a Bcl-2 family member, augments the development of inflammation-associated colorectal cancer
URI https://link.springer.com/article/10.1038/s41418-019-0383-9
https://www.ncbi.nlm.nih.gov/pubmed/31296963
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Volume 27
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