Transforming Growth Factor Beta Promotes Inflammation and Tumorigenesis in Smad4-Deficient Intestinal Epithelium in a YAP-Dependent Manner
Open accessAbstract
Transforming growth factor beta (TGF‐β), a multifunctional cytokine, plays critical roles in immune responses. However, the precise role of TGF‐β in colitis and colitis‐associated cancer remains poorly defined. Here, it is demonstrated that TGF‐β promotes the colonic inflammation and related tumorigenesis in the absence of Smad family member 4 (Smad4). Smad4 loss in intestinal epithelium aggravates colitis and colitis‐associated neoplasia induced by dextran sulfate sodium (DSS) and azoxymethane/dextran sulfate sodium (AOM/DSS), leading to over‐activated immune responses and increased TGF‐β 1 levels. In Smad4‐deficient organoids, TGF‐β 1 stimulates spheroid formation and impairs intestinal stem cell proliferation and lineage specification. YAP, whose expression is directly upregulated by TGF‐β 1 after Smad4 deletion, mediates the effect of TGF‐β 1 by interacting with Smad2/3. Attenuation of YAP/TAZ prevents TGF‐β 1‐induced spheroid formation in Smad4−/– organoids and alleviates colitis and colitis‐associated cancer in Smad4‐deficient mice. Collectively, these results highlight an integral role of the TGF‐β/Smad4 axis in restraining intestinal inflammation and tumorigenesis and suggest TGF‐β or YAP signaling as therapeutic targets for these gastrointestinal diseases intervention.
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SMAD4 deletion does not alter Paneth cell numbers during intestinal development in mice.
“This aligns with prior findings that SMAD4 deletion does not alter Paneth cell numbers during intestinal development in mice, suggesting that SMAD4 is not required for Paneth cell specification.55”
From Paneth-like transition drives resistance to dual targeting of KRAS and EGFR in colorectal cancer (2026) · cites this paper as [55]
The Results section reports no significant change in Paneth cell numbers after intestinal epithelial Smad4 deletion. However, the Experimental Section describes inducible deletion in mice generally aged 2–3 months; the paper does not establish the claimed finding during intestinal development. (LLM, conf=0.90)
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Cites
Identification of stem cells in small intestine and colon by marker gene Lgr5
Barker, N., van Es, J. H., Kuipers, J., Kujala, P., van den Born, M., Cozijnsen, M., Haegebarth, A., Korving, J., Begthel, H., Peters, P. J., et al. (2007) · Nature · doi:10.1038/nature06196 · Cited by 5,687 · see citing works
Sokol, H., Pigneur, B., Watterlot, L., Lakhdari, O., Bermúdez-Humarán, L. G., Gratadoux, J.-J., Blugeon, S., Bridonneau, C., Furet, J.-P., Corthier, G., et al. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0804812105 · Cited by 4,413 · see citing works
Intestinal epithelial cells: regulators of barrier function and immune homeostasis
Peterson, L. W., & Artis, D. (2014) · Nature reviews. Immunology · doi:10.1038/nri3608 · Cited by 3,191 · see citing works
The risk of colorectal cancer in ulcerative colitis: a meta-analysis
Eaden, J., Abrams, K. R., & Mayberry, J. F. (2001) · Gut · doi:10.1136/gut.48.4.526 · Cited by 2,948 · see citing works
Franke, A., McGovern, D. P. B., Barrett, J. C., Wang, K., Radford-Smith, G. L., Ahmad, T., Lees, C. W., Balschun, T., Lee, J., Roberts, R., et al. (2010) · Nature Genetics · doi:10.1038/ng.717 · Cited by 2,520 · see citing works
TEAD mediates YAP-dependent gene induction and growth control
Zhao, B., Ye, X., Yu, J., Li, L., Li, W., Li, S., Yu, J., Lin, J. D., Wang, C.-Y., Chinnaiyan, A. M., et al. (2008) · Genes & Development · doi:10.1101/gad.1664408 · Cited by 2,498 · see citing works
Transforming Growth Factor-β Signaling in Immunity and Cancer
Batlle, E., & Massagué, J. (2019) · Immunity · doi:10.1016/j.immuni.2019.03.024 · Cited by 2,366 · 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
Terzić, J., Grivennikov, S., Karin, E., & Karin, M. (2010) · Gastroenterology · doi:10.1053/j.gastro.2010.01.058 · Cited by 1,974 · see citing works
TGFβ drives immune evasion in genetically reconstituted colon cancer metastasis
Tauriello, D. V. F., Palomo-Ponce, S., Stork, D., Berenguer-Llergo, A., Badia-Ramentol, J., Iglesias, M., Sevillano, M., Ibiza, S., Cañellas, A., Hernando-Momblona, X., et al. (2018) · Nature · doi:10.1038/nature25492 · Cited by 1,851 · see citing works
Kaser, A., Zeissig, S., & Blumberg, R. S. (2010) · Annual Review of Immunology · doi:10.1146/annurev-immunol-030409-101225 · Cited by 1,806 · see citing works
Liu-Chittenden, Y., Huang, B., Shim, J. S., Chen, Q., Lee, S.-J., Anders, R. A., Liu, J. O., & Pan, D. (2012) · Genes & Development · doi:10.1101/gad.192856.112 · Cited by 1,452 · see citing works
The intestinal barrier: a fundamental role in health and disease
Vancamelbeke, M., & Vermeire, S. (2017) · Expert Review of Gastroenterology & Hepatology · doi:10.1080/17474124.2017.1343143 · Cited by 1,321 · see citing works
Anderson, C. A., Boucher, G., Lees, C. W., Franke, A., D’Amato, M., Taylor, K. D., Lee, J. C., Goyette, P., Imielinski, M. B., Latiano, A., et al. (2011) · Nature Genetics · doi:10.1038/ng.764 · Cited by 1,312 · see citing works
YAP1 increases organ size and expands undifferentiated progenitor cells
Camargo, F. D., Gokhale, S., Johnnidis, J. B., Fu, D., Bell, G. W., Jaenisch, R., & Brummelkamp, T. R. (2007) · Current Biology · doi:10.1016/j.cub.2007.10.039 · Cited by 1,252 · see citing works
The intestinal microbiota fuelling metabolic inflammation
Tilg, H., Zmora, N., Adolph, T. E., & Elinav, E. (2020) · Nature Reviews Immunology · doi:10.1038/s41577-019-0198-4 · Cited by 1,089 · see citing works
Tissue‐specific and inducible Cre‐mediated recombination in the gut epithelium
Marjou, F. E., Janssen, K., Chang, B. H., Li, M., Hindie, V., Chan, L., Louvard, D., Chambon, P., METZGER, D., & Robine, S. (2004) · genesis · doi:10.1002/gene.20042 · Cited by 1,044 · see citing works
Gorelik, L., & Flavell, R. A. (2000) · Immunity · doi:10.1016/s1074-7613(00)80170-3 · Cited by 959 · see citing works
Presence of adherent Escherichia coli strains in ileal mucosa of patients with Crohn's disease
Darfeuille–Michaud, A., Neut, C., Barnich, N., Lederman, E., Martino, P. D., Desreumaux, P., Gambiez, L. P., Joly, B., Cortot, A., & Colombel, J.-F. (1998) · Gastroenterology · doi:10.1016/s0016-5085(98)70019-8 · Cited by 859 · see citing works
TGF-β Activation and Function in Immunity
Travis, M. A., & Sheppard, D. (2014) · Annual Review of Immunology · doi:10.1146/annurev-immunol-032713-120257 · Cited by 856 · see citing works
High-fat diet enhances stemness and tumorigenicity of intestinal progenitors
Beyaz, S., Mana, M., Roper, J., Kedrin, D., Saadatpour, A., Hong, S., Bauer-Rowe, K. E., Xifaras, M. E., Akkad, A., Arias, E., et al. (2016) · Nature · doi:10.1038/nature17173 · Cited by 840 · see citing works
The Crumbs Complex Couples Cell Density Sensing to Hippo-Dependent Control of the TGF-β-SMAD Pathway
Varelas, X., Samavarchi‐Tehrani, P., Narimatsu, M., Weiss, A., Cockburn, K., Larsen, B. G., Rossant, J., & Wrana, J. L. (2010) · Developmental Cell · doi:10.1016/j.devcel.2010.11.012 · Cited by 683 · see citing works
YAP/TAZ-Dependent Reprogramming of Colonic Epithelium Links ECM Remodeling to Tissue Regeneration
Yui, S., Azzolin, L., Maimets, M., Pedersen, M. T., Fordham, R. P., Hansen, S. L., Larsen, H. L., Guiu, J., Alves, M. R. P., Rundsten, C. F., et al. (2017) · Cell stem cell · doi:10.1016/j.stem.2017.11.001 · Cited by 678 · see citing works
Self-citationCell fate specification and differentiation in the adult mammalian intestine
Beumer, J., & Clevers, H. C. (2020) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-020-0278-0 · Cited by 676 · see citing works
TAZ controls Smad nucleocytoplasmic shuttling and regulates human embryonic stem-cell self-renewal
Varelas, X., Sakuma, R., Samavarchi‐Tehrani, P., Peerani, R., Rao, B. M., Dembowy, J., Yaffe, M. B., Zandstra, P. W., & Wrana, J. L. (2008) · Nature Cell Biology · doi:10.1038/ncb1748 · Cited by 666 · see citing works
Thirty-Year Analysis of a Colonoscopic Surveillance Program for Neoplasia in Ulcerative Colitis
Rutter, M. D., Saunders, B. P., Wilkinson, K. H., Rumbles, S., Schofield, G., Kamm, M. A., Williams, C. B., Price, A. B., Talbot, I. C., & Forbes, A. (2006) · Gastroenterology · doi:10.1053/j.gastro.2005.12.035 · Cited by 645 · see citing works
Intestinal barrier dysfunction in inflammatory bowel diseases
McGuckin, M. A., Eri, R., Simms, L. A., Florin, T. H. J., & Radford-Smith, G. (2009) · Inflammatory Bowel Diseases · doi:10.1002/ibd.20539 · Cited by 627 · see citing works
Dow, L. E., O’Rourke, K. P., Simon, J. M., Tschaharganeh, D. F., van Es, J. H., Clevers, H. C., & Lowe, S. W. (2015) · Cell · doi:10.1016/j.cell.2015.05.033 · Cited by 549 · see citing works
SMAD4-dependent barrier constrains prostate cancer growth and metastatic progression
Ding, Z., Wu, C., Chu, G. C., Xiao, Y., Ho, D. C., Zhang, J., Perry, S. R., Labrot, E., Wu, X., Lis, R. T., et al. (2011) · Nature · doi:10.1038/nature09677 · Cited by 507 · see citing works
Self-citationThe Hippo signaling pathway restricts the oncogenic potential of an intestinal regeneration programPreprint
Cai, J., Zhang, N., Zheng, Y., de Wilde, R. F., Maitra, A., & Pan, D. (2010) · Genes & Development · doi:10.1101/gad.1978810 · Cited by 491 · see citing works
Inflammatory networks underlying colorectal cancer
Lasry, A., Zinger, A., & Ben‐Neriah, Y. (2016) · Nature Immunology · doi:10.1038/ni.3384 · Cited by 488 · see citing works
YAP/TAZ Are Mechanoregulators of TGF-β-Smad Signaling and Renal Fibrogenesis
Szeto, S. G., Narimatsu, M., Lu, M., He, X., Sidiqi, A. M., Tolosa, M. F., Chan, L., Freitas, K. D., Bialik, J. F., Majumder, S., et al. (2016) · Journal of the American Society of Nephrology · doi:10.1681/asn.2015050499 · Cited by 463 · see citing works
Zhou, D., Zhang, Y., Wu, H., Barry, E., Yin, Y., Lawrence, E., Dawson, D. M., Willis, J. E., Markowitz, S. D., Camargo, F. D., et al. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1110428108 · Cited by 453 · see citing works
Cell death in the gut epithelium and implications for chronic inflammation
Patankar, J. V., & Becker, C. (2020) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-020-0326-4 · Cited by 421 · see citing works
Autophagy negatively regulates Wnt signalling by promoting Dishevelled degradation
Gao, C., Cao, W., Bao, L., Zuo, W., Xie, G., Cai, T., Fu, W., Zhang, J., Wu, W., Zhang, X., et al. (2010) · Nature Cell Biology · doi:10.1038/ncb2082 · Cited by 385 · see citing works
Self-citationEllinghaus, D., Ellinghaus, E., Nair, R. P., Stuart, P. E., Esko, T., Metspalu, A., Debrus, S., Raelson, J., Tejasvi, T., Belouchi, M., et al. (2012) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2012.02.020 · Cited by 347 · see citing works
Parasitic helminths induce fetal-like reversion in the intestinal stem cell niche
Nusse, Y. M., Savage, A. K., Marangoni, P., Huber, A. R., Landman, T. A., de Sauvage, F. J., Locksley, R. M., & Klein, O. D. (2018) · Nature · doi:10.1038/s41586-018-0257-1 · Cited by 333 · see citing works
Qi, Z., Li, Y., Zhao, B., Xu, C., Liu, Y., Li, H., Zhang, B., Wang, X., Yang, X., Xie, W., et al. (2017) · Nature Communications · doi:10.1038/ncomms13824 · Cited by 320 · see citing works
Self-citationSmad4 signalling in T cells is required for suppression of gastrointestinal cancer
Kim, B., Li, C., Qiao, W., Mamura, M., Kasperczak, B., Anver, M. R., Wolfraim, L. A., Hong, S., Mushinski, E. B., Potter, M., et al. (2006) · Nature · doi:10.1038/nature04846 · Cited by 320 · see citing works
Immune regulation by fungal strain diversity in inflammatory bowel disease
Li, X. V., Leonardi, I., Putzel, G., Semon, A., Fiers, W. D., Kusakabe, T., Lin, W.-Y., Gao, I. H., Doron, I., Gutiérrez-Guerrero, A., et al. (2022) · Nature · doi:10.1038/s41586-022-04502-w · Cited by 303 · see citing works
Ihara, S., Hirata, Y., & Koike, K. (2017) · Journal of Gastroenterology · doi:10.1007/s00535-017-1350-1 · Cited by 300 · see citing works
Planell, N., Lozano, J. J., Mora‐Buch, R., Masamunt, M. C., Jimeno, M., Ordás, Í., Esteller, M., Ricart, E., Piqué, J. M., Panés, J., et al. (2012) · Gut · doi:10.1136/gutjnl-2012-303333 · Cited by 274 · see citing works
Vancamelbeke, M., Vanuytsel, T., Farré, R., Verstockt, S., Ferrante, M., Assche, G. V., Rutgeerts, P. J., Schuit, F. C., Vermeire, S., Arijs, I., et al. (2017) · Inflammatory Bowel Diseases · doi:10.1097/mib.0000000000001246 · Cited by 270 · see citing works
Generation of Smad4/Dpc4 conditional knockout mice
Yang, X. Y., Li, C., Herrera, P. L., & Deng, C. (2002) · genesis · doi:10.1002/gene.10029 · Cited by 231 · see citing works
Functional Hallmarks of Healthy Macrophage Responses: Their Regulatory Basis and Disease Relevance
Sheu, K. M., & Hoffmann, A. (2022) · Annual Review of Immunology · doi:10.1146/annurev-immunol-101320-031555 · Cited by 209 · see citing works
Sanjabi, S., Mosaheb, M. M., & Flavell, R. A. (2009) · Immunity · doi:10.1016/j.immuni.2009.04.020 · Cited by 193 · see citing works
Master regulator of intestinal disease: IL-6 in chronic inflammation and cancer development
Waldner, M. J., & Neurath, M. F. (2014) · Seminars in Immunology · doi:10.1016/j.smim.2013.12.003 · Cited by 193 · see citing works
Song, X., Gao, H., Lin, Y., Yao, Y., Zhu, S., Wang, J., Liu, Y., Yao, X., Meng, G., Shen, N., et al. (2014) · Immunity · doi:10.1016/j.immuni.2013.11.018 · Cited by 186 · see citing works
Cheung, P., Xiol, J., Dill, M. T., Yuan, W.-C., Panero, R., Roper, J., Osorio, F. G., Maglic, D., Li, Q., Gurung, B., et al. (2020) · Cell stem cell · doi:10.1016/j.stem.2020.07.003 · Cited by 185 · see citing works
Smad4-Mediated Signaling Inhibits Intestinal Neoplasia by Inhibiting Expression of β-Catenin
Freeman, T. J., Smith, J. J., Chen, X., Washington, M. K., Roland, J. T., Means, A. L., Eschrich, S. A., Yeatman, T. J., Deane, N. G., & Beauchamp, R. D. (2011) · Gastroenterology · doi:10.1053/j.gastro.2011.11.026 · Cited by 182 · see citing works
Inflammation and Colorectal Cancer
Long, A., Lundsmith, E. T., & Hamilton, K. E. (2017) · Current Colorectal Cancer Reports · doi:10.1007/s11888-017-0373-6 · Cited by 175 · see citing works
Transforming growth factor β: a master regulator of the gut microbiota and immune cell interactions
Bauché, D., & Marie, J. C. (2017) · Clinical & Translational Immunology · doi:10.1038/cti.2017.9 · Cited by 126 · see citing works
Gut Microbiota Protects against Gastrointestinal Tumorigenesis Caused by Epithelial Injury
Zhan, Y., Chen, P.-J., Sadler, W. D., Wang, F., Poe, S., Núñez, G., Eaton, K. A., & Chen, G. (2013) · Cancer Research · doi:10.1158/0008-5472.can-13-0827 · Cited by 106 · see citing works
The cellular niche for intestinal stem cells: a team effort
Zhu, G., Hu, J., & Xi, R. (2021) · Cell Regeneration · doi:10.1186/s13619-020-00061-5 · Cited by 97 · see citing works
Rani, R., Smulian, A. G., Greaves, D. R., Hogan, S. P., & Herbert, D. R. (2011) · European Journal of Immunology · doi:10.1002/eji.201041135 · Cited by 89 · see citing works
Hahn, J. N., Falck, V., & Jirik, F. R. (2011) · Journal of Clinical Investigation · doi:10.1172/jci45114 · Cited by 79 · see citing works
Lineage Reversion Drives WNT Independence in Intestinal Cancer
Han, T., Goswami, S., Hu, Y., Tang, F., Zafra, M. P., Murphy, C. J., Cao, Z., Poirier, J. T., Khurana, E., Elemento, O., et al. (2020) · Cancer Discovery · doi:10.1158/2159-8290.cd-19-1536 · Cited by 79 · see citing works
Intestinal epithelial plasticity and regeneration via cell dedifferentiation
Liu, Y., & Chen, Y. (2020) · Cell Regeneration · doi:10.1186/s13619-020-00053-5 · Cited by 79 · see citing works
Self-citationSMAD4 Suppresses WNT-Driven Dedifferentiation and Oncogenesis in the Differentiated Gut Epithelium
Perekatt, A. O., Shah, P., Cheung, S., Jariwala, N. H., Wu, A., Gandhi, V., Kumar, N., Feng, Q., Patel, N. R., Chen, L., et al. (2018) · Cancer Research · doi:10.1158/0008-5472.can-18-0043 · Cited by 77 · see citing works
Telomere dysfunction activates YAP1 to drive tissue inflammation
Chakravarti, D., Hu, B., Mao, X., Rashid, A., Li, J., Li, J., Liao, W., Whitley, E. M., Dey, P., Hou, P., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-18420-w · Cited by 75 · see citing works
Self-citationFoodborne intestinal flukes: A brief review of epidemiology and geographical distribution
Chai, J.-Y., & Jung, B.-K. (2019) · Acta Tropica · doi:10.1016/j.actatropica.2019.105210 · Cited by 57 · see citing works
Epithelial Smad4 Deletion Up-Regulates Inflammation and Promotes Inflammation-Associated Cancer
Means, A. L., Freeman, T. J., Zhu, J., Woodbury, L. G., Smith, P. M., Wu, C., Meyer, A. R., Weaver, C., Padmanabhan, C., An, H., et al. (2018) · Cellular and Molecular Gastroenterology and Hepatology · doi:10.1016/j.jcmgh.2018.05.006 · Cited by 57 · see citing works
Smith, P. M., Choksi, Y. A., Markham, N. O., Hanna, D. N., Zi, J., Weaver, C., Hamaamen, J. A., Lewis, K. B., Yang, J., Liu, Q., et al. (2021) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00053.2021 · Cited by 50 · see citing works
SMAD4 Suppresses Colitis-associated Carcinoma Through Inhibition of CCL20/CCR6-mediated Inflammation
Hanna, D. N., Smith, P. M., Novitskiy, S. V., Washington, M. K., Zi, J., Weaver, C., Hamaamen, J. A., Lewis, K. B., Zhu, J., Yang, J., et al. (2022) · Gastroenterology · doi:10.1053/j.gastro.2022.07.016 · Cited by 48 · see citing works
Inflammasomes in Colitis and Colorectal Cancer: Mechanism of Action and Therapies.
Pandey, A., Shen, C. X., & Man, S. M. (2019) · Europe PMC (PubMed Central) · Cited by 37 · see citing works
Chang, Y., Deng, Q., Zhang, Z., Zhao, H. Y., Tang, J., Chen, X., Liu, G., Tian, G., Cai, J., & Jia, G. (2020) · Journal of Cellular Physiology · doi:10.1002/jcp.30068 · Cited by 36 · see citing works
Role of SMAD proteins in colitis-associated cancer: from known to the unknown
Chandrasinghe, P. C., Cereser, B., Moorghen, M., Bakir, I. A., Tabassum, N., Hart, A., Stebbing, J., & Warusavitarne, J. H. (2017) · Oncogene · doi:10.1038/onc.2017.300 · Cited by 34 · see citing works
Hippo-Yap Signaling Maintains Sinoatrial Node Homeostasis
Zheng, M., Li, G., Song, J., Zhao, X., Tang, L., Erhardt, S., Chen, W., Nguyen, B. H., Li, X., Li, M., et al. (2022) · Circulation · doi:10.1161/circulationaha.121.058777 · Cited by 33 · see citing works
Igalouzene, R., Hernández‐Vargas, H., Benech, N., Guyennon, A., Bauché, D., Barrachina, C., Dubois, E., Marie, J. C., & Soudja, S. M. (2022) · Journal of Clinical Investigation · doi:10.1172/jci151020 · Cited by 31 · see citing works
Recent Advancement in Understanding Colitis-associated Tumorigenesis
Low, D., Mino-Kenudson, M. A., & Mizoguchi, E. (2014) · Inflammatory Bowel Diseases · doi:10.1097/mib.0000000000000094 · Cited by 28 · see citing works
IκBα deficiency imposes a fetal phenotype to intestinal stem cells
Marruecos, L., Bertran, J., Guillén, Y., González, J., Batlle, R., López‐Arribillaga, E., Garrido, M., Ruiz‐Herguido, C., Lisiero, D. N., Gonzàlez‐Farré, M., et al. (2019) · EMBO Reports · doi:10.15252/embr.201949708 · Cited by 19 · see citing works
Flagged first, then by citations
1 of the 72 references couldn’t be matched to a known paper.
Research works printed but not linked: 2
- [36]A. Pandey, C. Shen, S. M. Man, Yale J. Biol. Med. 2019, 92, 481. 31543710 PMC6747943
- [51]Y. Liu, Y. G. Chen, Cell Regener. 2020, 9, 14.
Cited by
Sorted by citations
Zhang, L., Ji, Q., Chen, Q., Wei, Z., Liu, S., Zhang, L., Zhang, Y., Li, Z., Liu, H., & Sui, H. (2023) · International Journal of Biological Sciences · doi:10.7150/ijbs.85712 · Cited by 78 · see citing works
Self-citationMechanical Stimulation of Anti‐Inflammatory and Antioxidant Hydrogels for Rapid Re‐Epithelialization
Yang, W., Zhong, W., Yan, S., Wang, S., Xuan, C., Zheng, K., Qiu, J., & Shi, X. (2024) · Advanced Materials · doi:10.1002/adma.202312740 · Cited by 48 · see citing works
Selenium Attenuates Radiation Colitis by Regulating cGAS‐STING Signaling
Xue, Q., Lai, H., Zhang, H., Li, G., Pi, F., Wu, Q., Liu, S., Yang, F., & Chen, T. (2024) · Advanced Science · doi:10.1002/advs.202403918 · Cited by 38 · see citing works
Wang, F., Ning, A., Sun, X., Zhou, Y., Deng, H., Zhou, H., Chen, S., He, M., Meng, Z., Wang, Y., et al. (2024) · Biomaterials · doi:10.1016/j.biomaterials.2024.122986 · Cited by 24 · see citing works
Self-citationPaneth-like transition drives resistance to dual targeting of KRAS and EGFR in colorectal cancer
Zhang, Y., Chen, J., She, Y., Fang, Z., Zhang, Y., Ruan, D., Guo, W., Liao, J., Zhou, W., Lao, J., et al. (2026) · Cancer Cell · doi:10.1016/j.ccell.2025.10.010 · Cited by 23 · see citing works
The role of intestinal macrophage polarization in colitis-associated colon cancer
Deng, Y., Jia, X., Liu, L., He, Q., & Liu, L. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1537631 · Cited by 21 · see citing works
Self-citationMechanotransduction in Shaping Immunity: Pathways, Crosstalk, and Pathophysiological Relevance
Yan, R., Li, Y., Chen, S., Zhu, L., Zhou, C., Chen, J., Zou, S., & Han, X. (2025) · Advanced Science · doi:10.1002/advs.202512164 · Cited by 20 · see citing works
Self-citationXu, T., Xiang, Y., Huang, Z., Zhu, Q., Wu, H., Cai, J., Weng, L., & Ge, H. (2025) · Journal of Ovarian Research · doi:10.1186/s13048-025-01757-5 · Cited by 19 · see citing works
Yu, L.-E., Yang, W., & Liang, Y. (2024) · Biomedicines · doi:10.3390/biomedicines12122771 · Cited by 13 · see citing works
Crotonate enhances intestinal regeneration after injury via HBO1-mediated H3K14 crotonylation
Xiao, Y., Yu, S., Zhang, M., Zhong, N., Hua, S., Fang, Z. H., Zhang, Z., Liu, H., Tan, R., Liu, Y., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-63869-2 · Cited by 11 · see citing works
Self-citationWang, H., Dhaliwal, N. S., Zahin, M., Zhao, T., Sims, G. L., Xie, J., & Zheng, G. (2025) · Integrative Medicine in Nephrology and Andrology · doi:10.1097/imna-d-24-00064 · Cited by 11 · see citing works
Song, M., Zhu, X., Zhao, X., Feng, J., & Sui, X. (2026) · Plants · doi:10.3390/plants15040575 · Cited by 10 · see citing works
The Role of Yes‐Associated Protein in Inflammatory Diseases and Cancer
Zhong, B., Du, J., Liu, F., & Sun, S. (2025) · MedComm · doi:10.1002/mco2.70128 · Cited by 10 · see citing works
Xu, X., & Foley, E. (2024) · Cell Reports · doi:10.1016/j.celrep.2024.113750 · Cited by 10 · see citing works
Wang, Z., Yang, C., Yan, S., Sun, J., Zhang, J., Qu, Z., Sun, W., Zang, J., & Xu, D. (2024) · Journal of Inflammation Research · doi:10.2147/jir.s488201 · Cited by 8 · see citing works
Zhang, Y., Zhang, Y., Yao, S., Chen, L., Dong, Q., Luo, R., Zheng, K., Liu, J., Liu, Y., Chen, Y., et al. (2025) · Phytotherapy Research · doi:10.1002/ptr.70015 · Cited by 7 · see citing works
Self-citationHippo signaling modulation and its biological implications in urological malignancies
Tong, T., Huang, M., Yan, B., Lin, B., Yu, J., Teng, Q., Li, P., & Pang, J. (2024) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2024.101280 · Cited by 7 · see citing works
Li, F., He, Z., Zhang, X., Gao, D., Xu, R. P., Zhang, Z., Cao, X., Shan, Q., Liu, Y., & Xu, Z. (2024) · Scientific Reports · doi:10.1038/s41598-024-74490-6 · Cited by 7 · see citing works
Zhang, Q.-Y., Lai, M.-Q., Chen, Y.-K., Zhong, M.-T., Gi, M., Wang, Q., & Xie, X. (2024) · Environmental Pollution · doi:10.1016/j.envpol.2024.124974 · Cited by 6 · see citing works
Self-citationLiu, J., Wang, Z.-Q., Chen, Y., Guo, Y., Li, X.-M., Li, Y., Zhang, P., Hou, X., Luo, C., Zhao, W., et al. (2025) · Aquaculture Reports · doi:10.1016/j.aqrep.2025.102875 · Cited by 4 · see citing works
Self-citationTGF-β signaling in organoids: The mechanisms and applications in 3D
Zhu, S., Liu, J., Qiu, X., Cai, G., & Gao, M. (2025) · Cell organoid (Print) · doi:10.26599/co.2025.9410015 · Cited by 4 · see citing works
Xu, L., Mo, Y., Yu, B., & Fan, S. (2025) · Discover Oncology · doi:10.1007/s12672-025-03157-z · Cited by 4 · see citing works
Mechanistic insights into intestinal stem cell disruption during infection
Chege, N., & Finney, C. A. M. (2025) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00352.2024 · Cited by 3 · see citing works
Epithelial-specific loss of Smad4 alleviates the fibrotic response in an acute colitis mouse model
Hashemi, Z., Hui, T., Wu, A., Matouba, D., Zukowski, S., Nejati, S., Lim, C., Bruzzese, J., Seabold, K., Mills, C., et al. (2024) · Life Science Alliance · doi:10.26508/lsa.202402935 · Cited by 2 · see citing works
Li, Y., Sun, R., Wang, X., Ma, M., Wang, H., Yang, B., Lu, Y., & Li, Y. (2025) · Journal of Inflammation Research · doi:10.2147/jir.s505313 · Cited by 2 · see citing works
Self-citationElkoshi, Z. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1704642 · Cited by 2 · see citing works
Ji, X., Ren, J., Dong, F., & Peng, W. (2024) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2024.1335395 · Cited by 2 · see citing works
Zhao, W., Hong, W., Dai, C., Li, B., Fu, Y., Cheng, J., & Li, H. (2025) · Microbial Pathogenesis · doi:10.1016/j.micpath.2025.107453 · Cited by 1 · see citing works
Fang, J., Gao, S., Wang, M., Wang, N., Du, J., Lin, W., & Lin, M. (2025) · Medicine · doi:10.1097/md.0000000000045385 · Cited by 1 · see citing works
Glycogen Hydrogel Loaded with Schistosoma japonicas Peptide SJMHE1 Improves Skin Wound Healing
Yang, Y., Wang, S., Jiang, Y., Huo, L., Zhu, W., Zhang, X., Zhang, Y., & Wang, X. (2026) · Biomolecules · doi:10.3390/biom16030392 · Cited by 1 · see citing works
Effects of SWI/SNF complex on DNA damage repair in heterochromatin of embryonic fibroblast cells
Zhang, H., Shu, Y., & Ji, M. (2023) · Radiation Medicine and Protection · doi:10.1016/j.radmp.2023.10.006 · Cited by 1 · see citing works
Chen, G., Chen, Z., Huang, S., Liu, Y., Lu, Z. J., Ou, G., Qi, Y., Wang, X., Wang, Y., Xie, W., et al. (2024) · Chinese Science Bulletin (Chinese Version) · doi:10.1360/tb-2024-0541 · Cited by 1 · see citing works
Self-citationStatus of Aqua MODIS Instrument On-Orbit Operation and Calibration
Xiong, J., Angal, A., Madhaven, S., Choi, J., Wenny, B. N., Sun, J., Wu, A., Chen, H., Salomonson, V. V., & Barnes, W. L. (2011) · NASA Technical Reports Server (NASA)
Jin, H., Zhang, M., Shi, M., Miao, P., & Zhang, M. (2025) · Molecular Carcinogenesis · doi:10.1002/mc.70048
SMAD4 May Serve as a Candidate Molecular Marker for Immune-Based Therapies Across Human Pan-Cancer
Liu, J., Lin, Y., Chen, X., & Huang, Z. (2025) · International Conference on Bioinformatics and Biomedical Technology (ICBBT) · doi:10.1109/icbbt65815.2025.11276658
Chen, W. L., Ge, M., Sun, S., Zhang, H., Wang, Z., Guo, Y., & Luo, Z. (2025) · Scientific Reports · doi:10.1038/s41598-025-32406-y
Zhao, Y.-H., Chen, J., Gong, T., Ge, H.-Y., & Li, M. (2026) · World Journal of Gastroenterology · doi:10.3748/wjg.v32.i11.113325
Tang, X. T., Jiang, N. J., Cui, Y., Shen, J., Lu, H., & Yan, F. (2026) · Scientific Reports · doi:10.1038/s41598-026-72151-4
Sun, X.-B., Zou, C., Li‐Ling, J., & Xie, H. (2026) · Biofabrication · doi:10.1088/1758-5090/ae7bc7
Si, C., Shu, L., Cao, W., Feng, Y., Dong, H., He, X., Yuan, J., Li, S., Cao, F., Zhu, Q. C., et al. (2026) · Journal of Food Biochemistry · doi:10.1155/jfbc/3245873
Chong, J., Ding, H., Ma, J., Gong, C., Xu, J., & Pan, J. (2026) · Naunyn-Schmiedeberg s Archives of Pharmacology · doi:10.1007/s00210-026-05749-0
Li, Y., Lai, R., He, Y., Cheng, L., Cheng, L., Yi, J., Li, Y., & Zhou, S. (2026) · Cells · doi:10.3390/cells15151396
Self-citation
- Authors
- Liu, L., Wang, Y., Yu, S., Liu, H., Li, Y., Hua, S., & Chen, Y.
- Affiliations
- Guangzhou Institutes of Biomedicine and Health (CN)
- Center for Life Sciences (CN)
- Yunnan University (CN)
- Nanchang University (CN)
- Corresponding author
- Chen, Ye‐Guang
- Venue
- Advanced Science
- Publisher
- Wiley
- Published
- 2023-06
- Volume
- 10
- Issue
- 23
- Pages
- e2300708-e2300708
- ISSN
- 2198-3844 (ISSN-L)
- PMC
- PMC10427365
- OpenAlex
- W4379056896
- Cited by
- 45
- References
- 72
- Citations by year
- 2026: 8 · 2025: 18 · 2024: 14 · 2023: 4
- FWCI
- 3.92
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Advanced Science (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Natural Science Foundation of China (31988101, 32000538)
- China Postdoctoral Science Foundation (2021M703230, 2022T150653)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Hippo pathway signaling and YAP/TAZ
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Wnt/β-catenin signaling in development and cancer
- Keywords
- TGF-beta, SMAD4, YAP, TAZ, colitis-associated colorectal cancer, intestinal inflammation, intestinal epithelium, Smad2/3 signaling, intestinal organoids, intestinal stem cells, spheroid formation, DSS-induced colitis, immune response, therapeutic target
- MeSH terms
- Colitis-Associated Neoplasms, Animals, Cell Transformation, Neoplastic, Colitis, Inflammation, Intestinal Mucosa, Transforming Growth Factor beta, Dextran Sulfate, Mice, Transforming Growth Factor beta1, Carcinogenesis
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