Pancreatic HIF2α Stabilization Leads to Chronic Pancreatitis and Predisposes to Mucinous Cystic Neoplasm

Heinis, 2010, Oxygen tension regulates pancreatic beta-cell differentiation through hypoxia-inducible factor 1alpha, Diabetes, 59, 662, 10.2337/db09-0891 Rahib, 2014, Projecting cancer incidence and deaths to 2030: the unexpected burden of thyroid, liver, and pancreas cancers in the United States, Cancer Res, 74, 2913, 10.1158/0008-5472.CAN-14-0155 Buchler, 2003, Hypoxia-inducible factor 1 regulates vascular endothelial growth factor expression in human pancreatic cancer, Pancreas, 26, 56, 10.1097/00006676-200301000-00010 Shi, 1999, Constitutive and inducible interleukin 8 expression by hypoxia and acidosis renders human pancreatic cancer cells more tumorigenic and metastatic, Clin Cancer Res, 5, 3711 Duffy, 2003, Influence of hypoxia and neoangiogenesis on the growth of pancreatic cancer, Mol Cancer, 2, 12, 10.1186/1476-4598-2-12 Semenza, 1992, A nuclear factor induced by hypoxia via de novo protein synthesis binds to the human erythropoietin gene enhancer at a site required for transcriptional activation, Mol Cell Biol, 12, 5447, 10.1128/MCB.12.12.5447 Wang, 1993, Characterization of hypoxia-inducible factor 1 and regulation of DNA binding activity by hypoxia, J Biol Chem, 268, 21513, 10.1016/S0021-9258(20)80571-7 Triner, 2016, Hypoxia-inducible factors: a central link between inflammation and cancer, J Clin Invest, 126, 3689, 10.1172/JCI84430 Wiesener, 2003, Widespread hypoxia-inducible expression of HIF-2alpha in distinct cell populations of different organs, FASEB J, 17, 271, 10.1096/fj.02-0445fje Lee, 2016, Hif1a deletion reveals pro-neoplastic function of B cells in pancreatic neoplasia, Cancer Discov, 6, 256, 10.1158/2159-8290.CD-15-0822 Chen, 2010, Impaired pancreatic development in Hif2-alpha deficient mice, Biochem Biophys Res Commun, 399, 440, 10.1016/j.bbrc.2010.07.111 Criscimanna, 2013, PanIN-specific regulation of Wnt signaling by HIF2alpha during early pancreatic tumorigenesis, Cancer Res, 73, 4781, 10.1158/0008-5472.CAN-13-0566 Lerch, 2013, Models of acute and chronic pancreatitis, Gastroenterology, 144, 1180, 10.1053/j.gastro.2012.12.043 Hezel, 2006, Genetics and biology of pancreatic ductal adenocarcinoma, Genes Dev, 20, 1218, 10.1101/gad.1415606 Ying, 2016, Genetics and biology of pancreatic ductal adenocarcinoma, Genes Dev, 30, 355, 10.1101/gad.275776.115 Kim, 2006, Failure to prolyl hydroxylate hypoxia-inducible factor alpha phenocopies VHL inactivation in vivo, EMBO J, 25, 4650, 10.1038/sj.emboj.7601300 Haase, 2001, Vascular tumors in livers with targeted inactivation of the von Hippel-Lindau tumor suppressor, Proc Natl Acad Sci U S A, 98, 1583, 10.1073/pnas.98.4.1583 Hingorani, 2003, Preinvasive and invasive ductal pancreatic cancer and its early detection in the mouse, Cancer Cell, 4, 437, 10.1016/S1535-6108(03)00309-X Flak, 2014, Leptin-inhibited PBN neurons enhance responses to hypoglycemia in negative energy balance, Nat Neurosci, 17, 1744, 10.1038/nn.3861 Collins, 2012, Oncogenic Kras is required for both the initiation and maintenance of pancreatic cancer in mice, J Clin Invest, 122, 639, 10.1172/JCI59227 Ferreira, 2015, Spontaneous pancreatitis caused by tissue-specific gene ablation of Hhex in mice, Cell Mol Gastroenterol Hepatol, 1, 550, 10.1016/j.jcmgh.2015.06.007 Kim, 2006, HIF-1-mediated expression of pyruvate dehydrogenase kinase: a metabolic switch required for cellular adaptation to hypoxia, Cell Metab, 3, 177, 10.1016/j.cmet.2006.02.002 Kopp, 2012, Identification of Sox9-dependent acinar-to-ductal reprogramming as the principal mechanism for initiation of pancreatic ductal adenocarcinoma, Cancer Cell, 22, 737, 10.1016/j.ccr.2012.10.025 Venkateshwari, 2011, Role of plasma MMP 9 levels in the pathogenesis of chronic pancreatitis, Indian J Clin Biochem, 26, 136, 10.1007/s12291-010-0103-1 Branton, 1999, TGF-beta and fibrosis, Microbes Infect, 1, 1349, 10.1016/S1286-4579(99)00250-6 Wouters, 2008, Hypoxia signalling through mTOR and the unfolded protein response in cancer, Nat Rev Cancer, 8, 851, 10.1038/nrc2501 Pereira, 2014, Endoplasmic reticulum (ER) stress and hypoxia response pathways interact to potentiate hypoxia-inducible factor 1 (HIF-1) transcriptional activity on targets like vascular endothelial growth factor (VEGF), J Biol Chem, 289, 3352, 10.1074/jbc.M113.507194 Hess, 2011, Extensive pancreas regeneration following acinar-specific disruption of Xbp1 in mice, Gastroenterology, 141, 1463, 10.1053/j.gastro.2011.06.045 Bi, 2005, ER stress-regulated translation increases tolerance to extreme hypoxia and promotes tumor growth, EMBO J, 24, 3470, 10.1038/sj.emboj.7600777 Sah, 2014, Endoplasmic reticulum stress is chronically activated in chronic pancreatitis, J Biol Chem, 289, 27551, 10.1074/jbc.M113.528174 Halbrook, 2017, Mitogen-activated protein kinase kinase activity maintains acinar-to-ductal metaplasia and is required for organ regeneration in pancreatitis, Cell Mol Gastroenterol Hepatol, 3, 99, 10.1016/j.jcmgh.2016.09.009 Zhang, 2013, Interleukin-6 is required for pancreatic cancer progression by promoting MAPK signaling activation and oxidative stress resistance, Cancer Res, 73, 6359, 10.1158/0008-5472.CAN-13-1558-T Nakamura, 2013, CCR2 knockout exacerbates cerulein-induced chronic pancreatitis with hyperglycemia via decreased GLP-1 receptor expression and insulin secretion, Am J Physiol Gastrointest Liver Physiol, 304, G700, 10.1152/ajpgi.00318.2012 Ewald, 2013, Diagnosis and treatment of diabetes mellitus in chronic pancreatitis, World J Gastroenterol, 19, 7276, 10.3748/wjg.v19.i42.7276 Makuc, 2016, Management of pancreatogenic diabetes: challenges and solutions, Diabetes Metab Syndr Obes, 9, 311, 10.2147/DMSO.S99701 Hart, 2016, Type 3c (pancreatogenic) diabetes mellitus secondary to chronic pancreatitis and pancreatic cancer, Lancet Gastroenterol Hepatol, 1, 226, 10.1016/S2468-1253(16)30106-6 Raimondi, 2010, Pancreatic cancer in chronic pancreatitis; aetiology, incidence, and early detection, Best Pract Res Clin Gastroenterol, 24, 349, 10.1016/j.bpg.2010.02.007 Izeradjene, 2007, Kras(G12D) and Smad4/Dpc4 haploinsufficiency cooperate to induce mucinous cystic neoplasms and invasive adenocarcinoma of the pancreas, Cancer Cell, 11, 229, 10.1016/j.ccr.2007.01.017 Lau, 2004, Differential expression of MUC1, MUC2, and MUC5AC in carcinomas of various sites: an immunohistochemical study, Am J Clin Pathol, 122, 61, 10.1309/9R6673QEC06D86Y4 Matthaei, 2011, Cystic precursors to invasive pancreatic cancer, Nat Rev Gastroenterol Hepatol, 8, 141, 10.1038/nrgastro.2011.2 Sano, 2014, Activated wnt signaling in stroma contributes to development of pancreatic mucinous cystic neoplasms, Gastroenterology, 146, 257, 10.1053/j.gastro.2013.09.044