Enteric bacterial protein AvrA promotes colonic tumorigenesis and activates colonic beta-catenin signaling pathway
Open accessAbstract
Salmonella infections can become chronic and increase the risk of cancer. The mechanisms by which specific Salmonella organisms contribute to cancer, however, are still unknown. Live and attenuated Salmonella are used as vectors to target cancer cells, but there have been no systematic studies of the oncogenic potential of chronic Salmonella infections in cancer models. AvrA, a pathogenic product of Salmonella, is inserted into host cells during infection and influences eukaryotic cell pathways. In the current study, we colonized mice with Salmonella AvrA-sufficient or AvrA-deficient Salmonella typhimirium strains and induced inflammation-associated colon cancer by azoxymethane/dextran sulfate sodium (AOM/DSS). We confirmed Salmonella persisted in the colon for up to 45 weeks. Salmonella was identified not only in epithelial cells on the colonic luminal surface and base of the crypts but also in invading tumors. Tumor incidence in the AvrA+infected group was 100% compared with 51.4% in the AOM/DSS group without bacterial gavage and 56.3% in mice infected with the AvrA- strain. Infection with AvrA+ strain also altered tumor distribution from the distal to proximal colon that might reflect changes in the microbiome. AvrA-expressing bacteria also upregulated beta-catenin signaling as assessed by decreased beta-catenin ubiquitination, increased nuclear beta-catenin and increased phosphorylated-beta-catenin (Ser552), a marker of proliferating stem-progenitor cells. Other β-catenin targets increased by AvrA included Bmi1, a cancer stem cell marker, matrix metalloproteinase-7, and cyclin D1. In summary, AvrA-expressing Salmonella infection activates β-catenin signals and enhances colonic tumorigenesis. Our findings provide important new mechanistic insights into how a bacterial protein targets proliferating stem-progenitor cells and contributes to cancer development. Our observations also raise a note of caution regarding the use of mutant Salmonella organisms as vectors for anti-cancer therapy. Finally, these studies could suggest biomarkers (such as AvrA level in gut) to assess cancer risk in susceptible individuals and infection-related dysregulation of β-catenin signaling in cancer.
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AvrA, a pathogenic product of Salmonella, has been shown to activate β-catenin signals and enhance colonic tumorigenesis.
“AvrA, a pathogenic product of Salmonella, has been shown to activate β-catenin signals and enhance colonic tumorigenesis.99”
From The gut microbiota and host health: a new clinical frontier (2016) · cites this paper as [99]
Salmonella enterica AvrA is able to translocate into host cells and activate β-catenin via its intrinsic de-ubiquitinase activity.
“In the same direction, the Salmonella enterica effector avirulence protein A (AvrA) is able to translocate into host’s cells and activate β-catenin via its intrinsic de-ubiquitinase activity [70].”
From Gut Microbiota and Cancer: From Pathogenesis to Therapy (2019) · cites this paper as [70]
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Coussens, L. M., & Werb, Z. (2002) · Nature · doi:10.1038/nature01322 · Cited by 15,111 · see citing works
Longitudinal Data Analysis for Discrete and Continuous Outcomes
Zeger, S. L., & Liang, K. (1986) · Biometrics · doi:10.2307/2531248 · Cited by 7,730 · see citing works
Intestinal inflammation targets cancer-inducing activity of the microbiota
Arthur, J. C., Perez-Chanona, E., Mühlbauer, M., Tomkovich, S., Uronis, J. M., Fan, T.-J., Campbell, B. J., Abujamel, T., Dogan, B., Rogers, A. B., et al. (2012) · Science · doi:10.1126/science.1224820 · Cited by 2,263 · see citing works
The cyclin D1 gene is a target of the β-catenin/LEF-1 pathway
Shtutman, M., Zhurinsky, J., Simcha, I., Albanese, C., D’Amico, M., Pestell, R., & Ben-Ze’ev, A. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.10.5522 · Cited by 2,230 · see citing works
Wu, S., Rhee, K.-J., Albesiano, E., Rabizadeh, S., Wu, X., Yen, H.-R., Huso, D. L., Brancati, F. L., Wick, E., McAllister, F., et al. (2009) · Nature Medicine · doi:10.1038/nm.2015 · Cited by 1,812 · see citing works
Self-citationSellon, R. K., Tonkonogy, S., Schultz, M., Dieleman, L. A., Grenther, W., Balish, E., Rennick, D. M., & Sartor, R. B. (1998) · Infection and Immunity · doi:10.1128/iai.66.11.5224-5231.1998 · Cited by 1,483 · see citing works
Bmi1 is expressed in vivo in intestinal stem cells
Sangiorgi, E., & Capecchi, M. R. (2008) · Nature Genetics · doi:10.1038/ng.165 · Cited by 1,192 · see citing works
Dieleman, L. A., Palmen, M. J. H. J., Akol, H., Bloemena, E., Peña, A. S., Meuwissen, S. G. M., & van Rees, E. P. (1998) · Clinical & Experimental Immunology · doi:10.1046/j.1365-2249.1998.00728.x · Cited by 1,167 · see citing works
Gastric Cancer Originating from Bone Marrow-Derived Cells
Houghton, J., Stoicov, C., Nomura, S., Rogers, A. B., Carlson, J. E., Li, H., Cai, X., Fox, J. G., Goldenring, J. R., & Wang, T. C. (2004) · Science · doi:10.1126/science.1099513 · Cited by 1,167 · see citing works
Mantovani, A. (2008) · Nature · doi:10.1038/457036b · Cited by 646 · see citing works
Haupt, Y., Alexander, W. S., Barri, G., Klinken, S. P., & Adams, J. M. (1991) · Cell · doi:10.1016/0092-8674(91)90383-a · Cited by 513 · see citing works
Pathology of mouse models of intestinal cancer: Consensus report and recommendations
Boivin, G. P., Washington, K. M., Yang, K., Ward, J. M., Pretlow, T. P., Russell, R. G., Besselsen, D. G., Godfrey, V., Doetschman, T. C., Dove, W. F., et al. (2003) · Gastroenterology · doi:10.1053/gast.2003.50094 · Cited by 496 · see citing works
Zhao, M. D., Yang, M., Li, X., Jiang, P., Baranov, E., Li, S., Xu, M., Penman, S., & Hoffman, R. M. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0408422102 · Cited by 488 · see citing works
McCormick, B. A., Colgan, S. P., Delp-Archer, C., Miller, S. I., & Madara, J. (1993) · The Journal of Cell Biology · doi:10.1083/jcb.123.4.895 · Cited by 447 · see citing works
Gradel, K. O., Nielsen, H. L., Schønheyder, H. C., Ejlertsen, T., Kristensen, B., & Nielsen, H. (2009) · Gastroenterology · doi:10.1053/j.gastro.2009.04.001 · Cited by 424 · see citing works
PTEN-deficient intestinal stem cells initiate intestinal polyposis
He, X., Yin, T., Grindley, J. C., Tian, Q., Sato, T., Tao, W. A., Dirisina, R., Porter-Westpfahl, K. S., Hembree, M. J., Johnson, T., et al. (2007) · Nature Genetics · doi:10.1038/ng1928 · Cited by 420 · see citing works
Self-citationThe IKK/NF-κB activation pathway—a target for prevention and treatment of cancer
Greten, F. R. (2003) · Cancer Letters · doi:10.1016/j.canlet.2003.08.029 · Cited by 410 · see citing works
Miller, S. I., & Mekalanos, J. J. (1990) · Journal of Bacteriology · doi:10.1128/jb.172.5.2485-2490.1990 · Cited by 399 · see citing works
Picco, M. F. (2010) · Yearbook of Gastroenterology · doi:10.1016/s0739-5930(09)79399-7 · Cited by 316 · see citing works
Collier-Hyams, L. S., Zeng, H., Sun, J., Tomlinson, A. D., Bao, Z., Chen, H., Madara, J., Orth, K., & Neish, A. S. (2002) · The Journal of Immunology · doi:10.4049/jimmunol.169.6.2846 · Cited by 276 · see citing works
Self-citationZhao, M. D., Geller, J., Ma, H., Yang, M., Penman, S., & Hoffman, R. M. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0703867104 · Cited by 246 · see citing works
Expanding role of ubiquitination in NF-κB signaling
Liu, S., & Chen, Z. J. (2010) · Cell Research · doi:10.1038/cr.2010.170 · Cited by 243 · see citing works
Vitamin D Receptor Negatively Regulates Bacterial-Stimulated NF-κB Activity in Intestine
Wu, S., Liao, A. P., Xia, Y., Li, Y. C., Li, J., Sartor, R. B., & Sun, J. (2010) · American Journal Of Pathology · doi:10.2353/ajpath.2010.090998 · Cited by 240 · see citing works
Self-citationIncreased NF-κB activity in fibroblasts lacking the vitamin D receptor
Sun, J., Kong, J., Duan, Y., Szeto, F. L., Liao, A. P., Madara, J., & Li, Y. C. (2006) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00590.2005 · Cited by 231 · see citing works
Self-citationSalmonella Effector AvrA Regulation of Colonic Epithelial Cell Inflammation by Deubiquitination
Ye, Z., Petrof, E. O., Boone, D. L., Claud, E. C., & Sun, J. (2007) · American Journal Of Pathology · doi:10.2353/ajpath.2007.070220 · Cited by 212 · see citing works
Self-citationHardt, W., & Galán, J. E. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.18.9887 · Cited by 212 · see citing works
Dammer, E. B., Na, C. H., Xu, P., Seyfried, N. T., Duong, D. M., Cheng, D., Gearing, M., Rees, H. D., Lah, J. J., Levey, A. I., et al. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.149633 · Cited by 182 · see citing works
β-Catenin activity negatively regulates bacteria-induced inflammation
Duan, Y., Liao, A. P., Kuppireddi, S., Ye, Z., Ciancio, M. J., & Sun, J. (2007) · Laboratory Investigation · doi:10.1038/labinvest.3700545 · Cited by 168 · see citing works
Self-citationChronic Enteric Salmonella Infection in Mice Leads to Severe and Persistent Intestinal Fibrosis
Graßl, G. A., Valdez, Y., Bergstrom, K., Vallance, B. A., & Finlay, B. B. (2008) · Gastroenterology · doi:10.1053/j.gastro.2007.12.043 · Cited by 157 · see citing works
Salmonella regulation of intestinal stem cells through the Wnt/β‐catenin pathway
Liu, X., Lu, R., Wu, S., & Sun, J. (2010) · FEBS Letters · doi:10.1016/j.febslet.2010.01.024 · Cited by 130 · see citing works
Self-citationCrosstalk between NF-κB and β-catenin pathways in bacterial-colonized intestinal epithelial cells
Sun, J., Hobert, M. E., Duan, Y., Rao, A. S., He, T., Chang, E. B., & Madara, J. (2005) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00515.2004 · Cited by 129 · see citing works
Self-citationLiao, A. P., Petrof, E. O., Kuppireddi, S., Zhao, Y., Xia, Y., Claud, E. C., & Sun, J. (2008) · PLoS ONE · doi:10.1371/journal.pone.0002369 · Cited by 121 · see citing works
Self-citationInfection as a risk factor for gallbladder cancer
Kumar, S., Kumar, S., & Kumar, S. (2006) · Journal of Surgical Oncology · doi:10.1002/jso.20530 · Cited by 119 · see citing works
Bacterial activation of β-catenin signaling in human epithelia
Sun, J., Hobert, M. E., Rao, A. S., Neish, A. S., & Madara, J. (2004) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00498.2003 · Cited by 105 · see citing works
Self-citationSelective Inhibition of Type III Secretion Activated Signaling by the Salmonella Effector AvrA
Du, F., & Galán, J. E. (2009) · PLoS Pathogens · doi:10.1371/journal.ppat.1000595 · Cited by 104 · see citing works
Sun, J., Mustafi, R., Cerda, S., Chumsangsri, A., Xia, Y., Li, Y. C., & Bissonnette, M. (2008) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2008.01.003 · Cited by 91 · see citing works
Self-citationChronic Effects of a Salmonella Type III Secretion Effector Protein AvrA In Vivo
Lu, R., Wu, S., Liu, X., Xia, Y., Zhang, Y., & Sun, J. (2010) · PLoS ONE · doi:10.1371/journal.pone.0010505 · Cited by 80 · see citing works
Self-citationSalmonella Promoters Preferentially Activated Inside Tumors
Arrach, N., Zhao, M. D., Porwollik, S., Hoffman, R. M., & McClelland, M. (2008) · Cancer Research · doi:10.1158/0008-5472.can-08-0552 · Cited by 78 · see citing works
Ricci‐Vitiani, L., Pagliuca, A., Palio, E., Zeuner, A., & Maria, R. D. (2008) · Gut · doi:10.1136/gut.2007.127837 · Cited by 72 · see citing works
Sellin, J. H., Umar, S., Xiao, J., & Morris, A. P. (2001) · PubMed · Cited by 71 · see citing works
Salmonella typhimurium infection increases p53 acetylation in intestinal epithelial cells
Wu, S., Ye, Z., Liu, X., Zhao, Y., Xia, Y., Steiner, A., Petrof, E. O., Claud, E. C., & Sun, J. (2010) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00526.2009 · Cited by 70 · see citing works
Self-citationLu, R., Liu, X., Wu, S., Xia, Y., Zhang, Y., Petrof, E. O., Claud, E. C., & Sun, J. (2012) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00453.2011 · Cited by 68 · see citing works
Self-citationBeta‐catenin activity negatively regulates bacteria‐induced inflammation
Sun, J., Duan, Y., Liao, A. P., Kuppireddi, S., Ye, Z., & Ciancio, M. J. (2007) · The FASEB Journal · doi:10.1096/fasebj.21.5.a589 · Cited by 66 · see citing works
Self-citationMyc is required for β-catenin-mediated mammary stem cell amplification and tumorigenesis
Moumen, M., Chiche, A., Decraene, C., Petit, V., Gandarillas, A., Deugnier, M., Glukhova, M. A., & Faraldo, M. M. (2013) · Molecular Cancer · doi:10.1186/1476-4598-12-132 · Cited by 55 · see citing works
Dougherty, U., Mustafi, R., Wang, Y., Musch, M. W., Wang, C., Konda, V. J. A., Kulkarni, A., Hart, J. A. L., Dawson, G., Kim, K. E., et al. (2011) · BMC Complementary and Alternative Medicine · doi:10.1186/1472-6882-11-111 · Cited by 48 · see citing works
Self-citationHu, D., Fang, W., Han, A., Gallagher, L., Davis, R. J., Xiong, B., & Yang, W. (2008) · Carcinogenesis · doi:10.1093/carcin/bgn239 · Cited by 45 · see citing works
Tao, Y., Hart, J. A. L., Lichtenstein, L., Joseph, L. J., Ciancio, M. J., Hu, S., Chang, E. B., & Bissonnette, M. (2008) · Carcinogenesis · doi:10.1093/carcin/bgn256 · Cited by 32 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
The gut microbiota and host health: a new clinical frontier
Marchesi, J. R., Adams, D. H., Fava, F., Hermes, G. D. A., Hirschfield, G. M., Hold, G., Quraishi, M. N., Kinross, J., Smidt, H., Tuohy, K. M., et al. (2016) · Gut · doi:10.1136/gutjnl-2015-309990 · Cited by 2,302 · see citing works
Garrett, W. S. (2015) · Science · doi:10.1126/science.aaa4972 · Cited by 1,404 · see citing works
The role of the microbiome in cancer development and therapy
Bhatt, A. P., Redinbo, M. R., & Bultman, S. J. (2017) · CA A Cancer Journal for Clinicians · doi:10.3322/caac.21398 · Cited by 653 · see citing works
Gut Microbiota and Cancer: From Pathogenesis to Therapy
Vivarelli, S., Salemi, R., Candido, S., Falzone, L., Santagati, M., Stefani, S., Torino, F., Banna, G. L., Tonini, G., & Libra, M. (2019) · Cancers · doi:10.3390/cancers11010038 · Cited by 586 · see citing works
The Intestinal Microbiota and Colorectal Cancer
Cheng, Y., Ling, Z., & Li, L. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.615056 · Cited by 588 · see citing works
Self-citation(2023) · doi:10.1038/s41392-022-01304-4 · Cited by 460 · see citing works
Self-citationMicrobiome, inflammation and colorectal cancer
Chen, J., Pitmon, E., & Wang, K. (2017) · Seminars in Immunology · doi:10.1016/j.smim.2017.09.006 · Cited by 267 · see citing works
Potential Role of the Gut Microbiome In Colorectal Cancer Progression
Kim, J.-H., & Lee, H. K. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2021.807648 · Cited by 269 · see citing works
Gut microbiota, inflammation and colorectal cancer
Sun, J., & Kato, I. (2016) · Genes & Diseases · doi:10.1016/j.gendis.2016.03.004 · Cited by 257 · see citing works
“Uninfected mice treated with AOM/DSS developed tumors in the distal colon.(150) In contrast, in mice infected with AvrAexpressing bacteria, tumors were found more in the proximal colon.”
BackgroundSelf-citationBacterial infections and cancer
van Elsland, D. M., & Neefjes, J. (2018) · EMBO Reports · doi:10.15252/embr.201846632 · Cited by 216 · see citing works
Yin, C., Noratto, G. D., Fan, X., Chen, Z., Yao, F., Shi, D., & Gao, H. (2020) · Carbohydrate Polymers · doi:10.1016/j.carbpol.2020.116942 · Cited by 216 · see citing works
The gastrointestinal microbiota and colorectal cancer
Keku, T. O., Dulal, S., Deveaux, A. E., Jovov, B., & Han, X. (2014) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00360.2012 · Cited by 205 · see citing works
Microbiota’s role in health and diseases
El-Sayed, A., Aleya, L., & Kamel, M. S. (2021) · Environmental Science and Pollution Research · doi:10.1007/s11356-021-14593-z · Cited by 195 · see citing works
Collateral damage: Insights into bacterial mechanisms that predispose host cells to cancer
Gagnaire, A., Nadel, B., Raoult, D., Neefjes, J., & Gorvel, J.-P. (2017) · Nature Reviews Microbiology · doi:10.1038/nrmicro.2016.171 · Cited by 189 · see citing works
The microbiome and the hallmarks of cancer
Fulbright, L. E., Ellermann, M., & Arthur, J. C. (2017) · PLOS Pathogens · doi:10.1371/journal.ppat.1006480 · Cited by 164 · see citing works
Epidemiology and risk factors of colorectal cancer in China
Yang, Y., Han, Z., Li, X., Huang, A., Shi, J., & Gu, J. (2020) · Chinese Journal of Cancer Research · doi:10.21147/j.issn.1000-9604.2020.06.06 · Cited by 138 · see citing works
Increased colon cancer risk after severe Salmonella infection
Mughini-Gras, L., Schaapveld, M., Kramers, J., Mooij, S., Neefjes-Borst, E. A., Pelt, W. V., & Neefjes, J. (2018) · PLoS ONE · doi:10.1371/journal.pone.0189721 · Cited by 133 · see citing works
Intestinal bacteria and colorectal cancer: etiology and treatment
Dougherty, M. W., & Jobin, C. (2023) · Gut Microbes · doi:10.1080/19490976.2023.2185028 · Cited by 138 · see citing works
Microbiome in cancer: Role in carcinogenesis and impact in therapeutic strategies
Rahman, M. M., Islam, M. R., Shohag, S., Ahasan, M. T., Sarkar, N., Khan, H., Hasan, A. M., Cavalu, S. D., & Rauf, A. (2022) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2022.112898 · Cited by 129 · see citing works
YopJ Family Effectors Promote Bacterial Infection through a Unique Acetyltransferase Activity
Ma, K., & Ma, W. (2016) · Microbiology and Molecular Biology Reviews · doi:10.1128/mmbr.00032-16 · Cited by 123 · see citing works
Salmonella Infection in Chronic Inflammation and Gastrointestinal Cancer
Zha, L., Garrett, S., & Sun, J. (2019) · Diseases · doi:10.3390/diseases7010028 · Cited by 113 · see citing works
Self-citationZhang, H., Jiang, F., Zhang, J., Wang, W., Li, L., & Yan, J. (2022) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2022.01.166 · Cited by 112 · see citing works
Self-citationCirculatory shear flow alters the viability and proliferation of circulating colon cancer cells
Fan, R., Emery, T., Zhang, Y., Xia, Y., Sun, J., & Wan, J. (2016) · Scientific Reports · doi:10.1038/srep27073 · Cited by 103 · see citing works
Self-citationGut microbiota-derived metabolites in CRC progression and causation
Dalal, N., Jalandra, R., Bayal, N., Yadav, A. K., Harshulika, Sharma, M., Makharia, G. K., Kumar, P., Singh, R. K., Solanki, P. R., et al. (2021) · Journal of Cancer Research and Clinical Oncology · doi:10.1007/s00432-021-03729-w · Cited by 102 · see citing works
Xu, H., Cao, C., Ren, Y., Weng, S., Liu, L., Guo, C., Wang, L., Han, X., Ren, J., & Liu, Z. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.949490 · Cited by 105 · see citing works
Salmonella protein AvrA activates the STAT3 signaling pathway in colon cancer
Lu, R., Wu, S., Zhang, Y.-G., Xia, Y., Zhou, Z., Kato, I., Dong, H., Bissonnette, M., & Sun, J. (2016) · Neoplasia · doi:10.1016/j.neo.2016.04.001 · Cited by 99 · see citing works
Self-citationAdapting Cancer Immunotherapy Models for the Real World
Klevorn, L. E., & Teague, R. M. (2016) · Trends in Immunology · doi:10.1016/j.it.2016.03.010 · Cited by 87 · see citing works
Gut Microbiota and Breast Cancer: The Dual Role of Microbes
Álvarez‐Mercado, A. I., Cano, A. D. V., Fernández, M. F., & Fontana, L. (2023) · Cancers · doi:10.3390/cancers15020443 · Cited by 88 · see citing works
STAT3 activation in infection and infection-associated cancer
Lu, R., Zhang, Y., & Sun, J. (2017) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2017.02.023 · Cited by 85 · see citing works
Self-citationMicrobiome-driven carcinogenesis in colorectal cancer: Models and mechanisms
Wang, X., Yang, Y., & Huycke, M. M. (2016) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2016.10.504 · Cited by 82 · see citing works
Lu, R., Bosland, M., Xia, Y., Zhang, Y.-G., Kato, I., & Sun, J. (2017) · Oncotarget · doi:10.18632/oncotarget.19052 · Cited by 75 · see citing works
Self-citationSpeaking the host language: how Salmonella effector proteins manipulate the host
Pillay, T. D., Hettiarachchi, S. U., Gan, J., Diaz-del-Olmo, I., Yu, X., Muench, J. H., Thurston, T. L. M., & Pearson, J. S. (2023) · Microbiology · doi:10.1099/mic.0.001342 · Cited by 70 · see citing works
Potential Impacts of Prebiotics and Probiotics on Cancer Prevention
Samanta, S. (2020) · Anti-Cancer Agents in Medicinal Chemistry · doi:10.2174/1871520621999201210220442 · Cited by 72 · see citing works
Rezasoltani, S., Yadegar, A., Aghdaei, H. A., & Zali, M. R. (2020) · Cancer Medicine · doi:10.1002/cam4.3694 · Cited by 66 · see citing works
Imbalance of autophagy and apoptosis in intestinal epithelium lacking the vitamin D receptor
Lu, R., Zhang, Y., Xia, Y., & Sun, J. (2019) · The FASEB Journal · doi:10.1096/fj.201900727r · Cited by 67 · see citing works
Self-citationZhu, R., Lang, T., Yan, W., Zhu, X. G., Huang, X. Y., Yin, Q., & Li, Y. (2021) · Advanced Science · doi:10.1002/advs.202003542 · Cited by 65 · see citing works
Zhang, S., Chen, X., Hu, Y., Wu, J., Cao, Q., Chen, S., & Gao, Y. (2015) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2015.12.018 · Cited by 64 · see citing works
Noncanonical Activation of β-Catenin by Porphyromonas gingivalis
Zhou, Y., Sztukowska, M. N., Wang, Q., Inaba, H., Potempa, J., Scott, D. A., Wang, H., & Lamont, R. J. (2015) · Infection and Immunity · doi:10.1128/iai.00302-15 · Cited by 63 · see citing works
Schistosoma japonicum–Associated Colorectal Cancer: A Review
Hamid, H. K. S. (2018) · American Journal of Tropical Medicine and Hygiene · doi:10.4269/ajtmh.18-0807 · Cited by 62 · see citing works
Gut Microbiota in Lung Cancer: Where Do We Stand?
Georgiou, K. E., Marinov, B. I., Farooqı, A. A., & Gazouli, M. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms221910429 · Cited by 60 · see citing works
The effect of the intratumoral microbiome on tumor occurrence, progression, prognosis and treatment
Gao, F., Yu, B., Rao, B., Sun, Y. H., Yu, J., Wang, D., Cui, G., & Ren, Z. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.1051987 · Cited by 61 · see citing works
The intratumoral microbiome: Characterization methods and functional impact
Heymann, C. J. F., Bard, J., Heymann, M., Heymann, D., & Bobin‐Dubigeon, C. (2021) · Cancer Letters · doi:10.1016/j.canlet.2021.09.009 · Cited by 58 · see citing works
Bacterial Manipulation of Wnt Signaling: A Host-Pathogen Tug-of-Wnt
Rogan, M. R., Patterson, L. L., Wang, J. Y., & McBride, J. W. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.02390 · Cited by 57 · see citing works
Bacteria as a double-action sword in cancer
Yaghoubi, A., Khazaei, M., Jalili, S., Hasanian, S. M., Avan, A., Soleimanpour, S., & Cho, W. C. S. (2020) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2020.188388 · Cited by 55 · see citing works
Alcohol Injury Damages Intestinal Stem Cells
Lu, R., Voigt, R. M., Zhang, Y., Kato, I., Xia, Y., Forsyth, C. B., Keshavarzian, A., & Sun, J. (2017) · Alcoholism Clinical and Experimental Research · doi:10.1111/acer.13351 · Cited by 56 · see citing works
Self-citationBacterial‐Mediated Tumor Therapy: Old Treatment in a New Context
Liu, Y., Niu, L., Li, N., Wang, Y., Liu, M., Su, X., Bao, X., Yin, B., & Shen, S. (2023) · Advanced Science · doi:10.1002/advs.202205641 · Cited by 55 · see citing works
The gut dysbiosis-cancer axis: illuminating novel insights and implications for clinical practice
Asseri, A. H., Bakhsh, T., Abuzahrah, S. S., Ali, S., & Rather, I. A. (2023) · Frontiers in Pharmacology · doi:10.3389/fphar.2023.1208044 · Cited by 54 · see citing works
Luo, T., Dunphy, P. S., Lina, T. T., & McBride, J. W. (2015) · Infection and Immunity · doi:10.1128/iai.01289-15 · Cited by 54 · see citing works
Integration of multi-omics approaches in exploring intra-tumoral heterogeneity
Dong, M.-M., Wang, L.-P., Hu, N., Rao, Y.-L., Wang, Z., & Zhang, Y. (2025) · Cancer Cell International · doi:10.1186/s12935-025-03944-2 · Cited by 49 · see citing works
Self-citationFrom DNA Damage to Cancer Progression: Potential Effects of Cytolethal Distending Toxin
Lai, Y.-R., Chang, Y., Ma, J., Chiu, C., Kuo, M., & Lai, C. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.760451 · Cited by 52 · see citing works
The tumor microbiome in cancer progression: mechanisms and therapeutic potential
Zhang, W., Xiang, Y., Ren, H., Liu, Y., Wang, Q., Ran, M., Zhou, W., Lu, T., Zheng, X., Qiao, C., et al. (2025) · Molecular Cancer · doi:10.1186/s12943-025-02403-w · Cited by 55 · see citing works
Profiling the Bladder Microbiota in Patients With Bladder Cancer
Parra-Grande, M., Oré-Arce, M., Martinez-Priego, L., D’Auria, G., Rossello-Mora, R. A., Lillo, M., Sempere, A., Lumbreras, B., & Sánchez, V. (2022) · Frontiers in Microbiology · doi:10.3389/fmicb.2021.718776 · Cited by 50 · see citing works
Deubiquitinases: Novel Therapeutic Targets in Immune Surveillance?
López‐Castejón, G., & Edelmann, M. J. (2016) · Mediators of Inflammation · doi:10.1155/2016/3481371 · Cited by 48 · see citing works
Sphyris, N., Hodder, M. C., & Sansom, O. J. (2021) · Cancers · doi:10.3390/cancers13051000 · Cited by 45 · see citing works
Microbiota in cancer: molecular mechanisms and therapeutic interventions
Chen, Z., Guan, D., Wang, Z., Li, X., Dong, S., Huang, J., & Zhou, W. (2023) · MedComm · doi:10.1002/mco2.417 · Cited by 46 · see citing works
Bacterial protein toxins in human cancers
Rosadi, F., Fiorentini, C., & Fabbri, A. (2015) · Pathogens and Disease · doi:10.1093/femspd/ftv105 · Cited by 46 · see citing works
Novel Regulatory Roles of Wnt1 in Infection-Associated Colorectal Cancer
Wang, J., Lu, R., Fu, X., Dan, Z., Zhang, Y., Chang, X., Liu, Q., Xia, Y., Liu, X., & Sun, J. (2018) · Neoplasia · doi:10.1016/j.neo.2018.03.001 · Cited by 45 · see citing works
Self-citationRole of Inflammation in Pathophysiology of Colonic Disease: An Update
Nasef, N. A., & Mehta, S. Y. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21134748 · Cited by 45 · see citing works
The Four Horsemen in Colon Cancer
Hernández-Luna, M. A., López-Briones, S., & Lurı́a-Pérez, R. (2019) · Journal of Oncology · doi:10.1155/2019/5636272 · Cited by 44 · see citing works
Microbe–MUC1 Crosstalk in Cancer-Associated Infections
Bose, M., & Mukherjee, P. (2019) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2019.10.003 · Cited by 44 · see citing works
Bacteriotherapy in gastrointestinal cancer
Soleimanpour, S., Hasanian, S. M., Avan, A., Yaghoubi, A., & Khazaei, M. (2020) · Life Sciences · doi:10.1016/j.lfs.2020.117754 · Cited by 43 · see citing works
Dey, P., & Chaudhuri, S. R. (2022) · Biology · doi:10.3390/biology11050757 · Cited by 42 · see citing works
Unveiling the intratumoral microbiota within cancer landscapes
Che, S., Yan, Z., Feng, Y., & Hai, Z. (2024) · iScience · doi:10.1016/j.isci.2024.109893 · Cited by 40 · see citing works
Digestive disorders and Intestinal microbiota.
Nouvenne, A., Ticinesi, A., Tana, C., Prati, B., Catania, P., Miraglia, C., Angelis, G. L. D., Mario, F. D., & Meschi, T. (2018) · Acta bio-medica dell'Ateneo parmense/Acta biomedica · doi:10.23750/abm.v89i9-s.7912 · Cited by 39 · see citing works
Gut Bacteria and their Metabolites: Which One Is the Defendant for Colorectal Cancer?
Tarashi, S., Siadat, S. D., Badi, S. A., Zali, M. R., Biassoni, R., Ponzoni, M., & Moshiri, A. (2019) · Microorganisms · doi:10.3390/microorganisms7110561 · Cited by 39 · see citing works
Oral and intestinal bacterial exotoxins: Potential linked to carcinogenesis
Silbergleit, M., Vasquez, A. A., Miller, C. J., Sun, J., & Kato, I. (2020) · Progress in molecular biology and translational science · doi:10.1016/bs.pmbts.2020.02.004 · Cited by 39 · see citing works
Self-citationMicrobiota, Epithelium, Inflammation, and TGF-β Signaling: An Intricate Interaction in Oncogenesis
Pang, X., Tang, Y.-J., Ren, X., Chen, Q., Tang, Y., & Liang, X. (2018) · Frontiers in Microbiology · doi:10.3389/fmicb.2018.01353 · Cited by 37 · see citing works
A Prognostic Model Based on the Immune-related Genes in Colon Adenocarcinoma
Sun, Y., Zhang, Y., Guo, Y., Yang, Z.-H., & Xu, Y. (2020) · International Journal of Medical Sciences · doi:10.7150/ijms.45813 · Cited by 36 · see citing works
Self-citationThe intestinal microbiome and surgical disease
Krezalek, M. A., Skowron, K. B., Guyton, K. L., Shakhsheer, B. A., Hyoju, S. K., & Alverdy, J. C. (2016) · Current Problems in Surgery · doi:10.1067/j.cpsurg.2016.06.001 · Cited by 32 · see citing works
The gastrointestinal microbiota in colorectal cancer cell migration and invasion
Henstra, C., van Praagh, J., Olinga, P., & Nagelkerke, A. (2021) · Clinical & Experimental Metastasis · doi:10.1007/s10585-021-10130-x · Cited by 32 · see citing works
Impact of bacterial infection and intestinal microbiome on colorectal cancer development
Sun, J. (2022) · Chinese Medical Journal · doi:10.1097/cm9.0000000000001979 · Cited by 33 · see citing works
Self-citationUbiquitination as an Efficient Molecular Strategy Employed in Salmonella Infection
Narayanan, L. A., & Edelmann, M. J. (2014) · Frontiers in Immunology · doi:10.3389/fimmu.2014.00558 · Cited by 32 · see citing works
Estrada, L. H., Wu, H., Ling, K., Zhang, G., Sumagin, R., Parkos, C. A., Jones, R. M., Champion, J. A., & Neish, A. S. (2017) · ACS Nano · doi:10.1021/acsnano.7b03239 · Cited by 32 · see citing works
Bacterial infection and microbiota in carcinogenesis and tumor development
Li, Q. (2023) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2023.1294082 · Cited by 31 · see citing works
Rastogi, Y. R., Saini, A. K., Thakur, V. K., & Saini, R. V. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21093212 · Cited by 30 · see citing works
van Elsland, D. M., Duijster, J. W., Zhang, J., Stévenin, V., Zhang, Y., Zha, L., Xia, Y., Franz, E., Sun, J., Mughini‐Gras, L., et al. (2022) · Cell Reports Medicine · doi:10.1016/j.xcrm.2022.100852 · Cited by 29 · see citing works
Self-citationBacterial translocation and barrier dysfunction enhance colonic tumorigenesis
Zhang, Y., Zhang, J., Xia, Y., & Sun, J. (2022) · Neoplasia · doi:10.1016/j.neo.2022.100847 · Cited by 28 · see citing works
Self-citationZNF281 Promotes Growth and Invasion of Pancreatic Cancer Cells by Activating Wnt/β-Catenin Signaling
Qian, Y., Li, J., & Xia, S. (2017) · Digestive Diseases and Sciences · doi:10.1007/s10620-017-4611-1 · Cited by 27 · see citing works
Microbiome Crosstalk in Immunotherapy and Antiangiogenesis Therapy
Wan, X., Song, M., Wang, A., Zhao, Y., Wei, Z., & Lu, Y. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.747914 · Cited by 26 · see citing works
Chakraborty, P., Aravindhan, V., & Mukherjee, S. (2023) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2023.124649 · Cited by 27 · see citing works
The intricate connection between diet, microbiota, and cancer: A jigsaw puzzle
Arkan, M. C. (2017) · Seminars in Immunology · doi:10.1016/j.smim.2017.08.009 · Cited by 25 · see citing works
Suppression of β‐catenin signaling in colon carcinoma cells by a bacterial protein
Nadeem, A., Aung, K. M., Ray, T., Alam, A., Persson, K., Pal, A., Uhlin, B. E., & Wai, S. N. (2021) · International Journal of Cancer · doi:10.1002/ijc.33562 · Cited by 25 · see citing works
Epidemiology and early screening strategies for colorectal cancer in China
Yang, Y., Gao, Z., Huang, A., Shi, J., Sun, Z. Z., Hong, H., & Gu, J. (2023) · Chinese Journal of Cancer Research · doi:10.21147/j.issn.1000-9604.2023.06.05 · Cited by 23 · see citing works
Cancer microbiota: a focus on tumor-resident bacteria
Vella, G., & Rescigno, M. (2025) · EMBO Reports · doi:10.1038/s44319-025-00482-w · Cited by 25 · see citing works
Activation of epigenetic regulator KDM6B by Salmonella Typhimurium enables chronic infections
Rana, S., Maurya, S., Mohapatra, G., Singh, S., Babar, R., Chandrasekhar, H., Chamoli, G., Rathore, D. K., Kshetrapal, P., & Srikanth, C. V. (2021) · Gut Microbes · doi:10.1080/19490976.2021.1986665 · Cited by 20 · see citing works
Gut microbiota in cancer initiation, development and therapy
Zhang, R., Zhang, X., Lau, H. C.-H., & Yu, J. Q. (2024) · Science China Life Sciences · doi:10.1007/s11427-024-2831-x · Cited by 19 · see citing works
Liu, W., Ruan, T., Ji, X., Ran, D., Sun, J. F., Shi, H., Prinz, R. A., Sun, J., Pan, Z., Jiao, X., et al. (2020) · Cellular Microbiology · doi:10.1111/cmi.13211 · Cited by 19 · see citing works
Self-citationLi, J., Zakariah, M., Malik, A., Ola, M. S., Syed, R., Chaudhary, A. A., & Khan, S. (2020) · Infection and Drug Resistance · doi:10.2147/idr.s258037 · Cited by 19 · see citing works
Progress in the Study of Colorectal Cancer Caused by Altered Gut Microbiota After Cholecystectomy
Ma, Y., Qu, R., Zhang, Y., Jiang, C., Zhang, Z., & Fu, W. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.815999 · Cited by 21 · see citing works
Self-citationXie, Y.-K., Ding, D., Wang, H.-M., & Kang, C.-J. (2015) · Fish & Shellfish Immunology · doi:10.1016/j.fsi.2015.08.030 · Cited by 17 · see citing works
Xu, X., Dai, Y., Feng, L., Zhang, H., Hu, Y., Xu, L., Zhu, X., & Jiang, Y. (2020) · Acta Biochimica et Biophysica Sinica · doi:10.1093/abbs/gmaa021 · Cited by 17 · see citing works
Khan, A. A., & Bano, Y. (2021) · Microbial Pathogenesis · doi:10.1016/j.micpath.2021.105011 · Cited by 17 · see citing works
The Gut Virome: A Neglected Actor in Colon Cancer Pathogenesis
Renuka, R., & Dahiya, D. K. (2017) · Future Microbiology · doi:10.2217/fmb-2017-0159 · Cited by 17 · see citing works
Rogan, M. R., Patterson, L. L., Byerly, C. D., Luo, T., Paessler, S., Veljković, V., Quade, B. R., & McBride, J. W. (2021) · mSphere · doi:10.1128/msphere.00216-21 · Cited by 17 · see citing works
Dysregulation of Bmi1 promotes malignant transformation of hepatic progenitor cells
Zhang, R., Wu, W., Shi, X.-D., Xu, L. B., Zhu, M.-S., Zeng, H., & Liu, C. (2016) · Oncogenesis · doi:10.1038/oncsis.2016.6 · Cited by 17 · see citing works
Intratumoral microbiota: implications for cancer progression and treatment
Xie, Z., Wu, Z., Liu, Y., Gu, Y., Niu, J., & Lv, K. (2025) · Frontiers in Microbiology · doi:10.3389/fmicb.2025.1551515 · Cited by 15 · see citing works
Zhang, L., & Yu, L. (2024) · Medicine · doi:10.1097/md.0000000000038078 · Cited by 15 · see citing works
Path to bacteriotherapy: From bacterial engineering to therapeutic perspectives
Liu, J., He, C., Tan, W., & Zheng, J. H. (2024) · Life Sciences · doi:10.1016/j.lfs.2024.122897 · Cited by 15 · see citing works
TRAF4 promotes the growth and invasion of colon cancer through the Wnt/β-catenin pathway.
Yang, K., Wang, F., & Han, J. (2015) · Europe PMC (PubMed Central) · Cited by 15 · see citing works
Microbiota in digestive cancers: our new partner?
Lopez, A., Hansmannel, F., Kökten, T., Bronowicki, J., Melhem, H., Sokol, H., & Peyrin‐Biroulet, L. (2017) · Carcinogenesis · doi:10.1093/carcin/bgx087 · Cited by 15 · see citing works
- Authors
- Lu, R., Wu, S., Zhang, Y.-G., Xia, Y., Liu, X., Zheng, Y., Chen, H., Schaefer, K. L., Zhou, Z., Bissonnette, M., Li, L., & Sun, J.
- Affiliations
- Rush University (US)
- University of Rochester (US)
- University of Rochester Medicine (US)
- University of Chicago (US)
- Stowers Institute for Medical Research (US)
- Corresponding author
- Sun, J
- Venue
- Oncogenesis
- Published
- 2014-06-09
- Volume
- 3
- Issue
- 6
- Pages
- e105-e105
- ISSN
- 2157-9024 (ISSN-L)
- PMC
- PMC4150214
- OpenAlex
- W1968540478
- Cited by
- 206
- References
- 47
- Citations by year
- 2026: 18 · 2025: 22 · 2024: 21 · 2023: 27 · 2022: 16 · 2021: 26 · 2020: 18 · 2019: 9 · 2018: 11 · 2017: 13 · 2016: 10 · 2015: 13 · 2014: 2
- FWCI
- 10.74
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Oncogenesis (publishedVersion, cc-by-nc-sa)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- Funders
- American Cancer Society
- National Cancer Institute (R01CA164124)
- National Institute of Diabetes and Digestive and Kidney Diseases (K01DK075386, DK075386, KO1-DK-075386)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biotechnology › Cancer Research and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Wnt/β-catenin signaling in development and cancer
- Life Sciences › Agricultural and Biological Sciences › Food Science › Salmonella and Campylobacter epidemiology
- Keywords
- avrA, Salmonella typhimurium, colon carcinogenesis, β-catenin signaling, chronic bacterial infection, cancer stem cells, BMI1, matrix metalloproteinase-7, cyclin D1, stem/progenitor cells, gut microbiota
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