Superfund Research Program

Effects of Superfund Toxicants on Liver Cancer Progenitor Cells

Project Leader: Michael Karin
Grant Number: P42ES010337
Funding Period: 2000-2017

Project-Specific Links

Publications

2017

• Chen S, Lu W, Yueh MF, Rettenmeier E, Liu M, Auwerx J, Yu RT, Evans RM, Wang K, Karin M, Tukey RH. 2017. Intestinal NCoR1, a regulator of epithelial cell maturation, controls neonatal hyperbilirubinemia. Proc Natl Acad Sci U S A 114(8):E1432-E1440. doi:10.1073/pnas.1700232114 PMID:28167773 PMCID:PMC5338369
• Shalapour S, Lin X, Bastian IN, Brain J, Burt AD, Aksenov AA, Vrbanac AF, Li W, Perkins A, Matsutani T, Zhong Z, Dhar D, Navas-Molina JA, Xu J, Loomba R, Downes M, Yu RT, Evans RM, Dorrestein PC, Knight R, Benner CW, Anstee QM, Karin M. 2017. Inflammation-induced IgA+ cells dismantle anti-liver cancer immunity. Nature 551(7680):340-345. doi:10.1038/nature24302 PMID:29144460 PMCID:PMC5884449

2016

• Duran A, Hernandez ED, Reina-Campos M, Castilla EA, Subramaniam S, Raghunandan S, Roberts LR, Kisseleva T, Karin M, Diaz-Meco MT, Moscat J. 2016. p62/SQSTM1 by binding to vitamin D receptor inhibits hepatic stellate cell activity, fibrosis, and liver cancer. Cancer Cell 30(4):595-609. doi:10.1016/j.ccell.2016.09.004 PMID:27728806 PMCID:PMC5081228
• Hee Lee J, Cho U, Karin M. 2016. Sestrin regulation of TORC1: Is Sestrin a leucine sensor?. Sci Signal 9(431):re5. doi:10.1126/scisignal.aaf2885 PMID:27273098 PMCID:PMC4902175
• Karin M, Clevers H. 2016. Reparative inflammation takes charge of tissue regeneration. Nature 529(7586):307-315. doi:10.1038/nature17039 PMID:26791721 PMCID:PMC5228603
• Karin M, Dhar D. 2016. Liver carcinogenesis: from naughty chemicals to soothing fat and the surprising role of NRF2. Carcinogenesis 37(6):541-546. doi:10.1093/carcin/bgw060 PMID:27207669 PMCID:PMC4876993
• Moscat J, Karin M, Diaz-Meco MT. 2016. p62 in cancer: signaling adaptor beyond autophagy. Cell 167(3):606-609. doi:10.1016/j.cell.2016.09.030 PMID:27768885 PMCID:PMC5114003
• Taniguchi K, Yamachika S, He F, Karin M. 2016. p62/SQSTM1-Dr Jekyll and Mr Hyde that prevents oxidative stress but promotes liver cancer. FEBS Lett 590(15):2375-2397. doi:10.1002/1873-3468.12301 PMID:27404485 PMCID:PMC4983218
• Umemura A, He F, Taniguchi K, Nakagawa H, Yamachika S, Font-Burgada J, Zhong Z, Subramaniam S, Raghunandan S, Duran A, Linares JF, Reina-Campos M, Umemura S, Valasek MA, Seki E, Yamaguchi K, Koike K, Itoh Y, Diaz-Meco MT, Moscat J, Karin M. 2016. p62, upregulated during preneoplasia, induces hepatocellular carcinogenesis by maintaining survival of stressed HCC-initiating cells. Cancer Cell 29(6):935-948. doi:10.1016/j.ccell.2016.04.006 PMID:27211490 PMCID:PMC4907799
• Zhong Z, Umemura A, Sanchez-Lopez E, Liang S, Shalapour S, Wong J, He F, Boassa D, Perkins GA, Ali S, McGeough MD, Ellisman MH, Seki E, Gustafsson AB, Hoffman HM, Diaz-Meco MT, Moscat J, Karin M. 2016. NF-κB restricts inflammasome activation via elimination of damaged mitochondria. Cell 164(5):896-910. doi:10.1016/j.cell.2015.12.057 PMID:26919428 PMCID:PMC4769378

2015

• Antonucci L, Fagman JB, Kim J, Todoric J, Gukovsky I, Mackey MR, Ellisman MH, Karin M. 2015. Basal autophagy maintains pancreatic acinar cell homeostasis and protein synthesis and prevents ER stress. Proc Natl Acad Sci U S A 112(45):E6166-E6174. doi:10.1073/pnas.1519384112 PMID:26512112 PMCID:PMC4653219
• Finkin S, Yuan D, Stein I, Taniguchi K, Weber A, Unger K, Browning JL, Goossens N, Nakagawa S, Gunasekaran G, Schwartz ME, Kobayashi M, Kumada H, Berger M, Pappo O, Rajewsky K, Hoshida Y, Karin M, Heikenwalder M, Ben-Neriah Y, Pikarsky E. 2015. Ectopic lymphoid structures function as microniches for tumor progenitor cells in hepatocellular carcinoma. Nat Immunol 16(12):1235-1244. doi:10.1038/ni.3290 PMID:26502405 PMCID:PMC4653079
• Font-Burgada J, Shalapour S, Ramasamy S, Hsueh B, Rossell D, Umemura A, Taniguchi K, Nakagawa H, Valasek MA, Ye L, Kopp JL, Sander M, Carter H, Deisseroth K, Verma IM, Karin M. 2015. Hybrid periportal hepatocytes regenerate the injured liver without giving rise to cancer. Cell 162(4):766-779. doi:10.1016/j.cell.2015.07.026 PMID:26276631 PMCID:PMC4545590
• Yang YM, Roh YS, Seki E. 2015. MafG, a novel target of FXR that regulates bile acid homeostasis. Gastroenterology 149(7):1981-1983. doi:10.1053/j.gastro.2015.10.014 PMID:26501563 PMCID:PMC4744927

2014

• Dhar D, Seki E, Karin M. 2014. NCOA5, IL-6, type 2 diabetes, and HCC: the deadly quartet. Cell Metab 19(1):6-7. doi:10.1016/j.cmet.2013.12.010 PMID:24411937 PMCID:PMC3947913
• Inokuchi-Shimizu S, Park E, Roh Y, Yang L, Zhang B, Song J, Liang S, Pimienta M, Taniguchi K, Wu X, Asahina K, Lagakos W, Mackey MR, Akira S, Ellisman MH, Sears DD, Olefsky J, Karin M, Brenner DA, Seki E. 2014. TAK1-mediated autophagy and fatty acid oxidation prevent hepatosteatosis and tumorigenesis. J Clin Invest 124(8):3566-3578. doi:10.1172/JCI74068 PMID:24983318 PMCID:PMC4109552
• Moles A, Murphy L, Wilson C, Chakraborty JB, Fox C, Park E, Mann J, Oakley F, Howarth R, Brain JD, Masson S, Karin M, Seki E, Mann DA. 2014. A TLR2/S100A9/CXCL-2 signaling network is necessary for neutrophil recruitment in acute and chronic liver injury in the mouse. J Hepatol 60(4):782-791. doi:10.1016/j.jhep.2013.12.005 PMID:24333183 PMCID:PMC3960359
• Nakagawa H, Umemura A, Taniguchi K, Font-Burgada J, Dhar D, Ogata H, Zhong Z, Valasek MA, Seki E, Hidalgo J, Koike K, Kaufman RJ, Karin M. 2014. ER stress cooperates with hypernutrition to trigger TNF-dependent spontaneous HCC development. Cancer Cell 26(3):331-343. doi:10.1016/j.ccr.2014.07.001 PMID:25132496 PMCID:PMC4165611
• Parmigiani A, Nourbakhsh A, Ding B, Wang W, Kim YC, Akopiants K, Guan K, Karin M, Budanov AV. 2014. Sestrins inhibit mTORC1 kinase activation through the GATOR complex. Cell Rep 9(4):1281-1291. doi:10.1016/j.celrep.2014.10.019 PMID:25457612 PMCID:PMC4303546
• Umemura A, Park E, Taniguchi K, Lee J, Shalapour S, Valasek MA, Aghajan M, Nakagawa H, Seki E, Hall MN, Karin M. 2014. Liver damage, inflammation, and enhanced tumorigenesis after persistent mTORC1 inhibition. Cell Metab 20(1):133-144. doi:10.1016/j.cmet.2014.05.001 PMID:24910242 PMCID:PMC4079758
• Yueh MF, Taniguchi K, Chen S, Evans RM, Hammock BD, Karin M, Tukey RH. 2014. The commonly used antimicrobial additive triclosan is a liver tumor promoter. Proc Natl Acad Sci U S A 111(48):17200-17205. doi:10.1073/pnas.1419119111 PMID:25404284 PMCID:PMC4260592

2013

• Chen S, Yueh MF, Bigo C, Barbier O, Wang K, Karin M, Nguyen N, Tukey RH. 2013. Intestinal glucuronidation protects against chemotherapy-induced toxicity by irinotecan (CPT-11). Proc Natl Acad Sci U S A 110(47):19143-19148. doi:10.1073/pnas.1319123110 PMID:24191041 PMCID:PMC3839688
• Du H, Sun X, Guma M, Luo J, Ouyang H, Zhang X, Zeng J, Quach J, Nguyen DH, Shaw PX, Karin M, Zhang K. 2013. JNK inhibition reduces apoptosis and neovascularization in a murine model of age-related macular degeneration. Proc Natl Acad Sci U S A 110(6):2377-2382. doi:10.1073/pnas.1221729110 PMID:23341606 PMCID:PMC3568328
• He G, Dhar D, Nakagawa H, Font-Burgada J, Ogata H, Jiang Y, Shalapour S, Seki E, Yost SE, Jepsen K, Frazer KA, Harismendy O, Hatziapostolou M, Iliopoulos D, Suetsugu A, Hoffman RM, Tateishi R, Koike K, Karin M. 2013. Identification of liver cancer progenitors whose malignant progression depends on autocrine IL-6 signaling. Cell 155(2):384-396. doi:10.1016/j.cell.2013.09.031 PMID:24120137 PMCID:PMC4015514
• Lee J, Budanov AV, Karin M. 2013. Sestrins orchestrate cellular metabolism to attenuate aging. Cell Metab 18(6):792-801. doi:10.1016/j.cmet.2013.08.018 PMID:24055102 PMCID:PMC3858445
• Sakurai T, Kudo M, Umemura A, He G, Elsharkawy AM, Seki E, Karin M. 2013. p38αlpha inhibits liver fibrogenesis and consequent hepatocarcinogenesis by curtailing accumulation of reactive oxygen species. Cancer Res 73(1):215-224. doi:10.1158/0008-5472.CAN-12-1602 PMID:23271722 PMCID:PMC3605785

2012

• Fujiwara R, Chen S, Karin M, Tukey RH. 2012. Reduced expression of UGT1A1 in intestines of humanized UGT1 mice via inactivation of NF-kappa B leads to hyperbilirubinemia. Gastroenterology 142:109-U259. doi:10.1053/j.gastro.2011.09.045 PMID:21983082 PMCID:PMC3428231
• Lee J, Budanov AV, Talukdar S, Park E, Park H, Park H, Bandyopadhyay G, Li N, Aghajan M, Jang I, Wolfe AM, Perkins GA, Ellisman MH, Bier E, Scadeng M, Foretz M, Viollet B, Olefsky J, Karin M. 2012. Maintenance of metabolic homeostasis by Sestrin 2 and Sestrin 3. Cell Metab 16(3):311-321. doi:10.1016/j.cmet.2012.08.004 PMID:22958918 PMCID:PMC3687365
• Seki E, Brenner DA, Karin M. 2012. A liver full of JNK: signaling in regulation of cell function and disease pathogenesis, and clinical approaches. Gastroenterology 143(2):307-320. doi:10.1053/j.gastro.2012.06.004 PMID:22705006 PMCID:PMC3523093
• Sun B, Karin M. 2012. Obesity, inflammation, and liver cancer. J Hepatol 56(3):704-713. doi:10.1016/j.jhep.2011.09.020 PMID:22120206 PMCID:PMC3889660
• Yu G, He G, Li C, Tang M, Grivennikov S, Tsai W, Wu M, Hsu C, Tsai Y, Wang L, Karin M. 2012. Hepatic expression of HCV RNA-dependent RNA polymerase triggers innate immune signaling and cytokine production. Mol Cell 48(2):313-321. doi:10.1016/j.molcel.2012.07.032 PMID:22959272 PMCID:PMC3483424

2011

• Hatziapostolou M, Polytarchou C, Aggelidou E, Drakaki A, Poultsides GA, Jaeger SA, Ogata H, Karin M, Struhl K, Hadzopoulou-Cladaras M, Iliopoulos D. 2011. An HNF4alpha-miRNA inflammatory feedback circuit regulates hepatocellular oncogenesis. Cell 147(6):1233-1247. doi:10.1016/j.cell.2011.10.043 PMID:22153071 PMCID:PMC3251960
• Holzer RG, Park E, Li N, Tran H, Chen M, Choi C, Solinas G, Karin M. 2011. Saturated fatty acids induce c-Src clustering within membrane subdomains, leading to JNK activation. Cell 147(1):173-184. doi:10.1016/j.cell.2011.08.034 PMID:21962514 PMCID:PMC3295636
• Koch KS, Leffert HL. 2011. Ectopic expression of CD74 in Ikk beta-deleted mouse hepatocytes. Acta Histochemica 113:428-435. doi:10.1016/j.acthis.2010.03.004 PMID:20569972 PMCID:PMC2965206
• Osterreicher C, Penz-Osterreicher M, Grivennikov S, Guma M, Koltsova E, Datz C, Sasik R, Hardiman G, Karin M, Brenner DA. 2011. Fibroblast-specific protein 1 identifies an inflammatory subpopulation of macrophages in the liver. Proc Natl Acad Sci U S A 108(1):308-313. doi:10.1073/pnas.1017547108 PMID:21173249 PMCID:PMC3017162

2010

• Bodmer R, Bier E, Karin M, Lee J. 2010. Sestrins at the crossroad between stress and aging. Aging-US 2(6):369-374. doi:10.18632/aging.100157 PMID:20606249 PMCID:PMC2919257
• Budanov AV, Lee J, Karin M. 2010. Stressin' Sestrins take an aging fight. EMBO Mol Med 2(10):388-400. doi:10.1002/emmm.201000097 PMID:20878915 PMCID:PMC3166214
• Park E, Lee J, Yu G, He G, Ali S, Holzer RG, Osterreicher CH, Takahashi H, Karin M. 2010. Dietary and genetic obesity promote liver inflammation and tumorigenesis by enhancing IL-6 and TNF expression. Cell 140(2):197-208. doi:10.1016/j.cell.2009.12.052 PMID:20141834 PMCID:PMC2836922

2009

• Haybaeck J, Zeller N, Wolf MJ, Weber A, Kurrer M, Bremer J, lezzi G, Graf R, Clavien P, Ndeospasov SA, Zatloukal K, Ramzan M, Ciesek S, Pietschmann T, Marche PN, Karin M, Kopf M, Browning JL, Aguzzi A, Heikenwalder M, Wagner U, Thimme R, Blum H. 2009. A lymphotoxin-driven pathway to hepatocellular carcinoma. Cancer Cell 16(4):295-308. doi:10.1016/j.ccr.2009.08.021 PMID:19800575 PMCID:PMC4422166
• Koch KS, Maeda S, Karin M, Leffert HL, He G. 2009. Targeted deletion of hepatocyte Ikkbeta confers growth advantages. Biochem Biophys Res Commun 380(2):349-354. doi:10.1016/j.bbrc.2009.01.085 PMID:19171122 PMCID:PMC2663043

2006

• Chang L, Kamata H, Solinas G, Luo J, Maeda S, Venuprasad K, Liu Y, Karin M. 2006. The E3 ubiquitin ligase itch couples JNK activation to TNF±-induced cell death by inducing c-FLIPL turnover. Cell 124:601-603. PMID:16469705
• Sakurai T, Maeda S, Chang L, Karin M. 2006. Loss of hepatic NF-kappa B activity enhances chemical hepatocarcinogenesis through sustained c-Jun N-terminal kinase 1 activation. Proc Natl Acad Sci U S A 103(28):10544-10551. doi:10.1073/pnas.0603499103 PMID:16807293 PMCID:PMC1502270

2005

• Kamata H, Honda S, Maeda S, Hirata H, Karin M. 2005. Reactive oxygen species promote TNFalpha-induced death and sustained JNK activation by inhibiting MAP kinase phosphatases. Cell 120(5):649-661. doi:10.1016/j.cell.2004.12.041 PMID:15766528
• Karin M, Greten FR. 2005. NF-ºB: Linking inflammmation and immunity to cancer development and progression. Nat Rev Immunol 5(10):749-759. PMID:16175180
• Maeda S, Kamata H, Luo J, Leffert HL, Karin M. 2005. IKKB couples hepatocyte death to cytokine-driven compensatory proliferation that promotes chemical hepatocarcinogenesis. Cell 121(7):977-990. PMID:15989949
• Zhang M, Joseph B, Gupta S, Guest I, Xu M, Sell S, Son K, Koch KS, Leffert HL. 2005. Embryonic mouse STO cell-derived xenografts express hepatocytic functions in the livers of nonimmunosuppressed adult rats. Stem Cells 23(2):186-199. PMID:15671142

2004

• Bonizzi G, Karin M. 2004. The two NF-kappaB activation pathways and their role in innate and adaptive immunity. Trends Immunol 25(6):280-288. PMID:15145317
• Galijatovic A, Beaton D, Nguyen N, Chen S, Bonzo JA, Johnson RS, Maeda S, Karin M, Guengerich FP, Tukey RH. 2004. The human CYP1A1 gene is regulated in a developmental and tissue-specific fashion in transgenic mice. J Biol Chem 279(23):23969-23976. PMID:15037607
• Greten FR, Eckmann L, Greten TF, Park JM, Li Z, Egan LJ, Kagnoff MF, Karin M. 2004. IKKB links inflammation and tumorigenesis in a mouse model of colitis-associated cancer. Cell 118(3):285-296. PMID:15294155
• Hsu L, Park JM, Zhang K, Luo J, Maeda S, Kaufman RJ, Eckmann L, Guiney DG, Karin M. 2004. The protein kinase PKR is required for macrophage apoptosis after activation of Toll-like receptor 4. Nature 428(6980):341-345. PMID:15029200
• Shen H, Lin Y, Choksi S, Tran JH, Jin T, Chang L, Karin M, Zhang J, Liu Z. 2004. Essential roles of receptor-interacting protein and TRAF2 in oxidative stress-induced cell death. Mol Cell Biol 24(13):5914-22. PMID:15199146
• Sil AK, Maeda S, Sano Y, Roop DR, Karin M. 2004. Abstract IkappaB kinase-alpha acts in the epidermis to control skeletal and craniofacial morphogenesis. Nature 428(6983):660-664. PMID:15071597
• Son K, Zhang M, Rucobo E, Nwaigwe D, Montgomery F, Leffert HL. 2004. Derivation and study of human epithelial cell lines resistant to killing by chromium trioxide. J Toxicol Environ Health A 67(13):1027-1049. PMID:15205032

2003

• Chen F, Castranova V, Li Z, Karin M, Shi X. 2003. Inhibitor of nuclear factor kappa B kinase deficiency enhances oxidative stress and prolongs c-jun NH2-terminal kinase activation induced by arsenic. Cancer Res 63(22):7689-7693. PMID:14633691
• Chen L, Egan LJ, Li Z, Kagnoff MF, Karin M. 2003. The two faces of IKK and NF-kappa B inhibition: prevention of systemic inflammation but increased local injury following intestinal ischemia-reperfusion. Nat Med 9(5):575-581. PMID:12692538
• Chen S, Nguyen N, Tamura K, Karin M, Tukey RH. 2003. The role of the Ah receptor and p38 in benzo[a]pyrene-7,8-dihydrodiol and benzo[a]pyrene-7,8-dihydrodiol-9,10-epoxide-induced apoptosis. J Biol Chem 278(21):19526-19533. PMID:12637498
• Hayakawa M, Miyashita H, Sakamoto I, Kitagawa M, Tanaka H, Yasuda H, Karin M, Kikugawa K. 2003. Evidence that reactive oxygen species do not mediate NF-kappa B activation. EMBO J 22(13July):3356-3366. PMID:12839997
• Li Z, Omori SA, Labuda T, Karin M, Rickert RC. 2003. IKK beta is required for peripheral B cell survival and proliferation. J Immunol 170(9):4630-4637. PMID:12707341
• Maeda S, Chang L, Li Z, Luo J, Leffert HL, Karin M. 2003. IKK beta is required for prevention of apoptosis mediated by cell-bound but not by circulating TNF alpha. Immunity 19(5):725-737. PMID:14614859
• Zhang L, Wang W, Hayashi Y, Jester JV, Birk DE, Gao M, Liu Y, Kao WW, Karin M, Xia Y. 2003. A role for MEK kinase 1 in TGF-beta/activin-induced epithelium movement and embryonic eyelid closure. EMBO J 22(17):4443-4454. doi:10.1093/emboj/cdg440 PMID:12941696 PMCID:PMC202382

2002

• Hirosumi J, Tuncman G, Chang L, Gorgun CZ, Uysal KT, Maeda K, Karin M, Hotamisligil GS. 2002. A central role for JNK in obesity and insulin resistance. Nature 420(6913):333-336. PMID:12447443
• Park JM, Greten FR, Li Z, Karin M. 2002. Macrophage apoptosis by anthrax lethal factor through p38 MAP kinase inhibition. Science 297(5589):2048-2051. PMID:12202685

2001

• Cao Y, Bonizzi G, Seagroves TN, Greten FR, Johnson RS, Schmidt EV, Karin M. 2001. IKK± provides an essential link between RANK signaling and cyclin D1 expression during mammary gland development. Cell 107:763-775. PMID:11747812
• Senftleben U, Cao Y, Xiao G, Greten FR, Krahn G, Bonizzi G, Chen Y, Hu Y, Fong A, Sun S, Karin M. 2001. Activation by IKKalpha of a second, evolutionary conserved, NF-kappa B signaling pathway. Science 293(5534):1495-1499. doi:10.1126/science.1062677 PMID:11520989
• Tang G, Minemoto Y, Dibling B, Purcell NH, Li Z, Karin M, Lin A. 2001. Inhibition of JNK activation by NF-kB target genes. Nature 414(6861):313-317. PMID:11713531

1989

• Hee Lee J, Cho U, Karin M. 1989. Discovery of 12-(S)-hydroxy-5,8,10,14-icosatetraenoic acid [12-(S)-HETE] in the tropical red alga Platysiphonia miniata. Sci Signal 37(2):303-308. PMID:2727309