Loss of Bcl-G, a Bcl-2 family member, augments the development of inflammation-associated colorectal cancer.
Journal
Cell death and differentiation
ISSN: 1476-5403
Titre abrégé: Cell Death Differ
Pays: England
ID NLM: 9437445
Informations de publication
Date de publication:
02 2020
02 2020
Historique:
received:
02
01
2019
accepted:
17
06
2019
revised:
06
06
2019
pubmed:
13
7
2019
medline:
2
7
2021
entrez:
13
7
2019
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 31296963
doi: 10.1038/s41418-019-0383-9
pii: 10.1038/s41418-019-0383-9
pmc: PMC7206067
doi:
Substances chimiques
BCL2L14 protein, human
0
Proto-Oncogene Proteins c-bcl-2
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
742-757Références
Ruemmele FM, Seidman EG, Lentze MJ. Regulation of intestinal epithelial cell apoptosis and the pathogenesis of inflammatory bowel disorders. J Pedia Gastroenterol Nutr. 2002;34:254–60.
doi: 10.1097/00005176-200203000-00005
Canli O, Nicolas AM, Gupta J, Finkelmeier F, Goncharova O, Pesic M, et al. Myeloid cell-derived reactive oxygen species induce epithelial mutagenesis. Cancer Cell. 2017;32:869. e865
pubmed: 29232557
doi: 10.1016/j.ccell.2017.11.004
Eaden JA, Abrams KR, Mayberry JF. The risk of colorectal cancer in ulcerative colitis: a meta-analysis. Gut. 2001;48:526–35.
pubmed: 11247898
pmcid: 1728259
doi: 10.1136/gut.48.4.526
Adams JM, Cory S. The BCL-2 arbiters of apoptosis and their growing role as cancer targets. Cell Death Differ. 2017;25:27.
pubmed: 29099483
pmcid: 5729526
doi: 10.1038/cdd.2017.161
Fletcher JI, Meusburger S, Hawkins CJ, Riglar DT, Lee EF, Fairlie WD, et al. Apoptosis is triggered when prosurvival Bcl-2 proteins cannot restrain Bax. Proc Natl Acad Sci USA. 2008;105:18081.
pubmed: 18981409
doi: 10.1073/pnas.0808691105
pmcid: 2577705
Letai A, Bassik MC, Walensky LD, Sorcinelli MD, Weiler S, Korsmeyer SJ. Distinct BH3 domains either sensitize or activate mitochondrial apoptosis, serving as prototype cancer therapeutics. Cancer Cell. 2002;2:183–92.
doi: 10.1016/S1535-6108(02)00127-7
pubmed: 12242151
Guo B, Godzik A, Reed JC. Bcl-G, a novel pro-apoptotic member of the Bcl-2 family. J Biol Chem. 2001;276:2780–5.
pubmed: 11054413
doi: 10.1074/jbc.M005889200
Giam M, Mintern JD, Rautureau GJ, Hinds MG, Strasser A, Bouillet P. Detection of Bcl-2 family member Bcl-G in mouse tissues using new monoclonal antibodies. Cell Death Dis. 2012;3:e378.
pubmed: 22914326
pmcid: 3434660
doi: 10.1038/cddis.2012.117
Giam M, Okamoto T, Mintern JD, Strasser A, Bouillet P. Bcl-2 family member Bcl-G is not a proapoptotic protein. Cell Death Dis. 2012;3:e404.
pubmed: 23059823
pmcid: 3481120
doi: 10.1038/cddis.2012.130
Kibel AS, Faith DA, Bova GS, Isaacs WB. Loss of heterozygosity at 12P12-13 in primary and metastatic prostate adenocarcinoma. J Urol. 2000;164:192–6.
pubmed: 10840458
doi: 10.1016/S0022-5347(05)67493-9
Aissani B, Bonan C, Baccichet A, Sinnett D. Childhood acute lymphoblastic leukemia: is there a tumor suppressor gene in chromosome 12p12.3? Leuk Lymphoma. 1999;34:231–9.
pubmed: 10439360
doi: 10.3109/10428199909050948
Hatta Y, Takeuchi S, Yokota J, Koeffler HP. Ovarian cancer has frequent loss of heterozygosity at chromosome 12p12.3-13.1 (region of TEL and Kip1 loci) and chromosome 12q23-ter: evidence for two new tumour-suppressor genes. Br J Cancer. 1997;75:1256–62.
pubmed: 9155043
pmcid: 2228239
doi: 10.1038/bjc.1997.214
Montpetit A, Boily G, Sinnett D. A detailed transcriptional map of the chromosome 12p12 tumour suppressor locus. Eur J Hum Genet. 2002;10:62–71.
pubmed: 11896457
doi: 10.1038/sj.ejhg.5200766
Neufert C, Becker C, Neurath MF. An inducible mouse model of colon carcinogenesis for the analysis of sporadic and inflammation-driven tumor progression. Nat Protoc. 2007;2:1998–2004.
pubmed: 17703211
doi: 10.1038/nprot.2007.279
Tanaka T, Suzuki R, Kohno H, Sugie S, Takahashi M, Wakabayashi K. Colonic adenocarcinomas rapidly induced by the combined treatment with 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine and dextran sodium sulfate in male ICR mice possess beta-catenin gene mutations and increases immunoreactivity for beta-catenin, cyclooxygenase-2 and inducible nitric oxide synthase. Carcinogenesis. 2005;26:229–38.
pubmed: 15459021
doi: 10.1093/carcin/bgh292
Wirtz S, Neufert C, Weigmann B, Neurath MF. Chemically induced mouse models of intestinal inflammation. Nat Protoc. 2007;2:541–6.
doi: 10.1038/nprot.2007.41
pubmed: 17406617
Moser AR, Pitot HC, Dove WF. A dominant mutation that predisposes to multiple intestinal neoplasia in the mouse. Sci (New York, NY). 1990;247:322–4.
doi: 10.1126/science.2296722
Yamada Y, Mori H. Multistep carcinogenesis of the colon in Apc(Min/ + ) mouse. Cancer Sci. 2007;98:6–10.
pubmed: 17052257
doi: 10.1111/j.1349-7006.2006.00348.x
Olsen J, Gerds TA, Seidelin JB, Csillag C, Bjerrum JT, Troelsen JT, et al. Diagnosis of ulcerative colitis before onset of inflammation by multivariate modeling of genome-wide gene expression data. Inflamm bowel Dis. 2009;15:1032–8.
pubmed: 19177426
doi: 10.1002/ibd.20879
Hussain SP, Amstad P, Raja K, Ambs S, Nagashima M, Bennett WP, et al. Increased p53 mutation load in noncancerous colon tissue from ulcerative colitis: a cancer-prone chronic inflammatory disease. Cancer Res. 2000;60:3333–7.
pubmed: 10910033
Kern SE, Redston M, Seymour AB, Caldas C, Powell SM, Kornacki S, et al. Molecular genetic profiles of colitis-associated neoplasms. Gastroenterology. 1994;107:420–8.
pubmed: 8039618
doi: 10.1016/0016-5085(94)90167-8
Yoshida T, Mikami T, Mitomi H, Okayasu I. Diverse p53 alterations in ulcerative colitis-associated low-grade dysplasia: full-length gene sequencing in microdissected single crypts. J Pathol. 2003;199:166–75.
pubmed: 12533829
doi: 10.1002/path.1264
Takaku H, Ajioka Y, Watanabe H, Hashidate H, Yamada S, Yokoyama J, et al. Mutations of p53 in morphologically non-neoplastic mucosa of long-standing ulcerative colitis. Jpn J Cancer Res. 2001;92:119–26.
pubmed: 11223540
pmcid: 5926702
doi: 10.1111/j.1349-7006.2001.tb01073.x
Fogt F, Vortmeyer AO, Goldman H, Giordano TJ, Merino MJ, Zhuang Z. Comparison of genetic alterations in colonic adenoma and ulcerative colitis-associated dysplasia and carcinoma. Hum Pathol. 1998;29:131–6.
pubmed: 9490271
doi: 10.1016/S0046-8177(98)90222-2
Fearon ER, Vogelstein B. A genetic model for colorectal tumorigenesis. Cell. 1990;61:759–67.
pubmed: 2188735
doi: 10.1016/0092-8674(90)90186-I
Miled C, Pontoglio M, Garbay S, Yaniv M, Weitzman JB. A genomic map of p53 binding sites identifies novel p53 targets involved in an apoptotic network. Cancer Res. 2005;65:5096–104.
pubmed: 15958553
doi: 10.1158/0008-5472.CAN-04-4232
Leroy B, Girard L, Hollestelle A, Minna JD, Gazdar AF, Soussi T. Analysis of TP53 mutation status in human cancer cell lines: a reassessment. Hum Mutat. 2014;35:756–65.
pubmed: 24700732
pmcid: 4451114
doi: 10.1002/humu.22556
Amcheslavsky A, Jiang J, Ip YT. Tissue damage-induced intestinal stem cell division in Drosophila. Cell Stem Cell. 2009;4:49–61.
pubmed: 19128792
pmcid: 2659574
doi: 10.1016/j.stem.2008.10.016
Kuraishy A, Karin M, Grivennikov SI. Tumor promotion via injury- and death-induced inflammation. Immunity. 2011;35:467–77.
pubmed: 22035839
pmcid: 3587290
doi: 10.1016/j.immuni.2011.09.006
Barker N, van Es JH, Kuipers J, Kujala P, van den Born M, Cozijnsen M, et al. Identification of stem cells in small intestine and colon by marker gene Lgr5. Nature. 2007;449:1003–7.
pubmed: 17934449
doi: 10.1038/nature06196
Vriesendorp HM, Vigneulle RM, Kitto G, Pelky T, Taylor P, Smith J. Survival after total body irradiation: effects of irradiation of exteriorized small intestine. Radiother Oncol. 1992;23:160–9.
pubmed: 1533466
doi: 10.1016/0167-8140(92)90326-P
Phesse TJ, Myant KB, Cole AM, Ridgway RA, Pearson H, Muncan V, et al. Endogenous c-Myc is essential for p53-induced apoptosis in response to DNA damage in vivo. Cell Death Differ. 2014;21:956–66.
pubmed: 24583641
pmcid: 4013513
doi: 10.1038/cdd.2014.15
Ernst M, Preaudet A, Putoczki T. Non-invasive Assessment of the Efficacy of New Therapeutics for Intestinal Pathologies Using Serial Endoscopic Imaging of Live Mice. J. Vis. Exp. 2015; e52383. https://doi.org/10.3791/52383 .
McGuckin MA, Linden SK, Sutton P, Florin TH. Mucin dynamics and enteric pathogens. Nat Rev Microbiol. 2011;9:265–78.
pubmed: 21407243
doi: 10.1038/nrmicro2538
Sheng YH, Hasnain SZ, Florin TH, McGuckin MA. Mucins in inflammatory bowel diseases and colorectal cancer. J Gastroenterol Hepatol. 2012;27:28–38.
pubmed: 21913981
doi: 10.1111/j.1440-1746.2011.06909.x
Johansson ME, Thomsson KA, Hansson GC. Proteomic analyses of the two mucus layers of the colon barrier reveal that their main component, the Muc2 mucin, is strongly bound to the Fcgbp protein. J Proteome Res. 2009;8:3549–57.
pubmed: 19432394
doi: 10.1021/pr9002504
Erickson NA, Nystrom EE, Mundhenk L, Arike L, Glauben R, Heimesaat MM, et al. The goblet cell protein Clca1 (Alias mClca3 or Gob-5) is not required for intestinal mucus synthesis, structure and barrier function in naive or DSS-challenged mice. PLoS ONE. 2015;10:e0131991.
pubmed: 26162072
pmcid: 4498832
doi: 10.1371/journal.pone.0131991
van der Meer-van Kraaij C, Kramer E, Jonker-Termont D, Katan MB, nvan der Meer R, Keijer J. Differential gene expression in rat colon by dietary heme and calcium. Carcinogenesis. 2005;26:73–9.
pubmed: 15539406
doi: 10.1093/carcin/bgh288
Veis DJ, Sorenson CM, Shutter JR, Korsmeyer SJ. Bcl-2-deficient mice demonstrate fulminant lymphoid apoptosis, polycystic kidneys, and hypopigmented hair. Cell. 1993;75:229–40.
pubmed: 8402909
doi: 10.1016/0092-8674(93)80065-M
Motoyama N, Wang F, Roth KA, Sawa H, Nakayama K, Nakayama K, et al. Massive cell death of immature hematopoietic cells and neurons in Bcl-x-deficient mice. Science. 1995;267:1506–10.
pubmed: 7878471
doi: 10.1126/science.7878471
Bouillet P, Metcalf D, Huang DC, Tarlinton DM, Kay TW, Kontgen F, et al. Proapoptotic Bcl-2 relative Bim required for certain apoptotic responses, leukocyte homeostasis, and to preclude autoimmunity. Science. 1999;286:1735–8.
doi: 10.1126/science.286.5445.1735
pubmed: 10576740
Knudson CM, Tung KS, Tourtellotte WG, Brown GA, Korsmeyer SJ. Bax-deficient mice with lymphoid hyperplasia and male germ cell death. Science. 1995;270:96–9.
pubmed: 7569956
doi: 10.1126/science.270.5233.96
Dirisina R, Katzman RB, Goretsky T, Managlia E, Mittal N, Williams DB, et al. p53 and PUMA independently regulate apoptosis of intestinal epithelial cells in patients and mice with colitis. Gastroenterology. 2011;141:1036–45.
pubmed: 21699775
doi: 10.1053/j.gastro.2011.05.032
Qiu W, Carson-Walter EB, Kuan SF, Zhang L, Yu J. PUMA suppresses intestinal tumorigenesis in mice. Cancer Res. 2009;69:4999–5006.
pubmed: 19491259
pmcid: 2872079
doi: 10.1158/0008-5472.CAN-09-0262
Scherr AL, Gdynia G, Salou M, Radhakrishnan P, Duglova K, Heller A, et al. Bcl-xL is an oncogenic driver in colorectal cancer. Cell Death Dis. 2016;7:e2342.
pubmed: 27537525
pmcid: 5108319
doi: 10.1038/cddis.2016.233
Yeretssian G, Correa RG, Doiron K, Fitzgerald P, Dillon CP, Green DR, et al. Non-apoptotic role of BID in inflammation and innate immunity. Nature. 2011;474:96–9.
pubmed: 21552281
doi: 10.1038/nature09982
Merritt AJ, Allen TD, Potten CS, Hickman JA. Apoptosis in small intestinal epithelial from p53-null mice: evidence for a delayed, p53-independent G2/M-associated cell death after gamma-irradiation. Oncogene. 1997;14:2759–66.
pubmed: 9190891
doi: 10.1038/sj.onc.1201126
Vogelstein B, Lane D, Levine AJ. Surfing the p53 network. Nature. 2000;408:307–10.
pubmed: 11099028
doi: 10.1038/35042675
Spehlmann ME, Manthey CF, Dann SM, Hanson E, Sandhu SS, Liu LY, et al. Trp53 deficiency protects against acute intestinal inflammation. J Immunol. 2013;191:837–47.
pubmed: 23772033
doi: 10.4049/jimmunol.1201716
Chang WC, Coudry RA, Clapper ML, Zhang X, Williams KL, Spittle CS, et al. Loss of p53 enhances the induction of colitis-associated neoplasia by dextran sulfate sodium. Carcinogenesis. 2007;28:2375–81.
pubmed: 17557903
doi: 10.1093/carcin/bgm134
Fujii S, Fujimori T, Kawamata H, Takeda J, Kitajima K, Omotehara F, et al. Development of colonic neoplasia in p53 deficient mice with experimental colitis induced by dextran sulphate sodium. Gut. 2004;53:710–6.
pubmed: 15082590
pmcid: 1774053
doi: 10.1136/gut.2003.028779
Allen A, Hutton DA, Pearson JP. The MUC2 gene product: a human intestinal mucin. Int J Biochem Cell Biol. 1998;30:797–801.
pubmed: 9722984
doi: 10.1016/S1357-2725(98)00028-4
Tytgat KM, Buller HA, Opdam FJ, Kim YS, Einerhand AW, Dekker J. Biosynthesis of human colonic mucin: Muc2 is the prominent secretory mucin. Gastroenterology. 1994;107:1352–63.
pubmed: 7926500
doi: 10.1016/0016-5085(94)90537-1
Yang B, Cao L, Liu B, McCaig CD, Pu J. The transition from proliferation to differentiation in colorectal cancer is regulated by the calcium activated chloride channel A1. PLoS ONE. 2013;8:e60861.
pubmed: 23593331
pmcid: 3625186
doi: 10.1371/journal.pone.0060861
Heazlewood CK, Cook MC, Eri R, Price GR, Tauro SB, Taupin D, et al. Aberrant mucin assembly in mice causes endoplasmic reticulum stress and spontaneous inflammation resembling ulcerative colitis. PLoS Med. 2008;5:e54.
pubmed: 18318598
pmcid: 2270292
doi: 10.1371/journal.pmed.0050054
Van der Sluis M, De Koning BA, De Bruijn AC, Velcich A, Meijerink JP, Van Goudoever JB, et al. Muc2-deficient mice spontaneously develop colitis, indicating that MUC2 is critical for colonic protection. Gastroenterology. 2006;131:117–29.
pubmed: 16831596
doi: 10.1053/j.gastro.2006.04.020
Wenzel UA, Magnusson MK, Rydstrom A, Jonstrand C, Hengst J, Johansson ME, et al. Spontaneous colitis in Muc2-deficient mice reflects clinical and cellular features of active ulcerative colitis. PLoS ONE. 2014;9:e100217.
pubmed: 24945909
pmcid: 4063762
doi: 10.1371/journal.pone.0100217
Zhang XN, Liu JX, Hu YW, Chen H, Yuan ZH. Hyper-activated IRF-1 and STAT1 contribute to enhanced interferon stimulated gene (ISG) expression by interferon alpha and gamma co-treatment in human hepatoma cells. Biochim Biophys Acta. 2006;1759:417–25.
pubmed: 16987558
doi: 10.1016/j.bbaexp.2006.08.003
Gupta BK, Maher DM, Ebeling MC, Sundram V, Koch MD, Lynch DW, et al. Increased expression and aberrant localization of mucin 13 in metastatic colon cancer. J Histochem Cytochem. 2012;60:822–31.
pubmed: 22914648
pmcid: 3524568
doi: 10.1369/0022155412460678
Shimamura T, Ito H, Shibahara J, Watanabe A, Hippo Y, Taniguchi H, et al. Overexpression of MUC13 is associated with intestinal-type gastric cancer. Cancer Sci. 2005;96:265–73.
pubmed: 15904467
doi: 10.1111/j.1349-7006.2005.00043.x
Walsh MD, Young JP, Leggett BA, Williams SH, Jass JR, McGuckin MA. The MUC13 cell surface mucin is highly expressed by human colorectal carcinomas. Hum Pathol. 2007;38:883–92.
pubmed: 17360025
doi: 10.1016/j.humpath.2006.11.020
Chauhan SC, Vannatta K, Ebeling MC, Vinayek N, Watanabe A, Pandey KK, et al. Expression and functions of transmembrane mucin MUC13 in ovarian cancer. Cancer Res. 2009;69:765–74.
pubmed: 19176398
doi: 10.1158/0008-5472.CAN-08-0587
Sheng YH, Lourie R, Linden SK, Jeffery PL, Roche D, Tran TV, et al. The MUC13 cell-surface mucin protects against intestinal inflammation by inhibiting epithelial cell apoptosis. Gut. 2011;60:1661–70.
pubmed: 21636645
doi: 10.1136/gut.2011.239194
Barrett T, Wilhite SE, Ledoux P, Evangelista C, Kim IF, Tomashevsky M, et al. NCBI GEO: archive for functional genomics data sets–update. Nucleic acids Res. 2013;41(Database issue):D991–5.
pubmed: 23193258
Wisniewski JR, Zougman A, Mann M. Combination of FASP and StageTip-based fractionation allows in-depth analysis of the hippocampal membrane proteome. J Proteome Res. 2009;8:5674–8.
pubmed: 19848406
doi: 10.1021/pr900748n
Delconte RB, Kolesnik TB, Dagley LF, Rautela J, Shi W, Putz EM, et al. CIS is a potent checkpoint in NK cell-mediated tumor immunity. Nat Immunol. 2016;17:816–24.
pubmed: 27213690
doi: 10.1038/ni.3470
Cox J, Neuhauser N, Michalski A, Scheltema RA, Olsen JV, Mann M. Andromeda: a peptide search engine integrated into the MaxQuant environment. J Proteome Res. 2011;10:1794–805.
pubmed: 21254760
doi: 10.1021/pr101065j
Cox J, Mann M. MaxQuant enables high peptide identification rates, individualized p.p.b.-range mass accuracies and proteome-wide protein quantification. Nat Biotechnol. 2008;26:1367–72.
pubmed: 19029910
doi: 10.1038/nbt.1511
Willert K, Brown JD, Danenberg E, Duncan AW, Weissman IL, Reya T, et al. Wnt proteins are lipid-modified and can act as stem cell growth factors. Nature. 2003;423:448.
pubmed: 12717451
doi: 10.1038/nature01611
Evans MJ, Hartman SL, Wolff DW, Rollins SA, Squinto SP. Rapid expression of an anti-human C5 chimeric Fab utilizing a vector that replicates in COS and 293 cells. J Immunol Methods. 1995;184:123–38.
pubmed: 7622864
doi: 10.1016/0022-1759(95)00093-P
Yip HYK, Tan CW, Hirokawa Y, Burgess AW. Colon organoid formation and cryptogenesis are stimulated by growth factors secreted from myofibroblasts. PLoS ONE. 2018;13:e0199412.
pubmed: 29928021
pmcid: 6013242
doi: 10.1371/journal.pone.0199412
Hirokawa Y, Yip KHY, Tan CW, Burgess AW. Colonic myofibroblast cell line stimulates colonoid formation. Am J Physiol-Gastrointest Liver Physiol. 2014;306:G547–56.
pubmed: 24481605
doi: 10.1152/ajpgi.00267.2013
Tan CW, Hirokawa Y, Burgess AW. Analysis of Wnt signalling dynamics during colon crypt development in 3D culture. Sci Rep. 2015;5:11036.
pubmed: 26087250
pmcid: 4471889
doi: 10.1038/srep11036