KDM6A Regulates Cell Plasticity and Pancreatic Cancer Progression by Noncanonical Activin Pathway

Mizrahi, 2020, Pancreatic cancer, Lancet, 395, 2008, 10.1016/S0140-6736(20)30974-0 Lippi, 2020, The global burden of pancreatic cancer, Arch Med Sci, 16, 820, 10.5114/aoms.2020.94845 Vakoc, 2017, Untangling the genetics from the epigenetics in pancreatic cancer metastasis, Nat Genet, 49, 323, 10.1038/ng.3798 Makohon-Moore, 2017, Limited heterogeneity of known driver gene mutations among the metastases of individual patients with pancreatic cancer, Nat Genet, 49, 358, 10.1038/ng.3764 Yachida, 2010, Distant metastasis occurs late during the genetic evolution of pancreatic cancer, Nature, 467, 1114, 10.1038/nature09515 Roe, 2017, Enhancer reprogramming promotes pancreatic cancer metastasis, Cell, 170, 875, 10.1016/j.cell.2017.07.007 Waddell, 2015, Whole genomes redefine the mutational landscape of pancreatic cancer, Nature, 518, 495, 10.1038/nature14169 Bailey, 2016, Genomic analyses identify molecular subtypes of pancreatic cancer, Nature, 531, 47, 10.1038/nature16965 Schulz, 2019, The histone demethylase UTX/KDM6A in cancer: progress and puzzles, Int J Cancer, 145, 614, 10.1002/ijc.32116 Ler, 2017, Loss of tumor suppressor KDM6A amplifies PRC2-regulated transcriptional repression in bladder cancer and can be targeted through inhibition of EZH2, Sci Transl Med, 9, eaai8312, 10.1126/scitranslmed.aai8312 Stief, 2020, Loss of KDM6A confers drug resistance in acute myeloid leukemia, Leukemia, 34, 50, 10.1038/s41375-019-0497-6 Taube, 2017, The H3K27me3-demethylase KDM6A is suppressed in breast cancer stem-like cells, and enables the resolution of bivalency during the mesenchymal-epithelial transition, Oncotarget, 8, 65548, 10.18632/oncotarget.19214 Soto, 2017, KDM6A addiction of cervical carcinoma cell lines is triggered by E7 and mediated by p21CIP1 suppression of replication stress, PLoS Pathog, 13, 10.1371/journal.ppat.1006661 Yu, 2019, GATA3 recruits UTX for gene transcriptional activation to suppress metastasis of breast cancer, Cell Death Dis, 10, 832, 10.1038/s41419-019-2062-7 Andricovich, 2018, Loss of KDM6A activates super-enhancers to induce gender-specific squamous-like pancreatic cancer and confers sensitivity to BET inhibitors, Cancer Cell, 33, 512, 10.1016/j.ccell.2018.02.003 Watanabe, 2019, Loss of KDM6A characterizes a poor prognostic subtype of human pancreatic cancer and potentiates HDAC inhibitor lethality, Int J Cancer, 145, 192, 10.1002/ijc.32072 Paulsen, 2014, Use of Bru-Seq and BruChase-Seq for genome-wide assessment of the synthesis and stability of RNA, Methods, 67, 45, 10.1016/j.ymeth.2013.08.015 Loomans, 2014, Intertwining of activin A and TGFβ signaling: dual roles in cancer progression and cancer cell invasion, Cancers (Basel), 7, 70, 10.3390/cancers7010070 Togashi, 2015, Activin signal promotes cancer progression and is involved in cachexia in a subset of pancreatic cancer, Cancer Lett, 356, 819, 10.1016/j.canlet.2014.10.037 Namwanje, 2016, Activins and inhibins: roles in development, physiology, and disease, Cold Spring Harb Perspect Biol, 8, a021881, 10.1101/cshperspect.a021881 Kawaguchi, 2002, The role of the transcriptional regulator Ptf1a in converting intestinal to pancreatic progenitors, Nat Genet, 32, 128, 10.1038/ng959 Tuveson, 2004, Endogenous oncogenic K-ras(G12D) stimulates proliferation and widespread neoplastic and developmental defects, Cancer Cell, 5, 375, 10.1016/S1535-6108(04)00085-6 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 Hingorani, 2005, Trp53R172H and KrasG12D cooperate to promote chromosomal instability and widely metastatic pancreatic ductal adenocarcinoma in mice, Cancer Cell, 7, 469, 10.1016/j.ccr.2005.04.023 Yadav, 2013, The epidemiology of pancreatitis and pancreatic cancer, Gastroenterology, 144, 1252, 10.1053/j.gastro.2013.01.068 Guerra, 2007, Chronic pancreatitis is essential for induction of pancreatic ductal adenocarcinoma by K-Ras oncogenes in adult mice, Cancer Cell, 11, 291, 10.1016/j.ccr.2007.01.012 Azizi, 2021, Loss of activating transcription factor 3 prevents KRAS-mediated pancreatic cancer, Oncogene, 40, 3118, 10.1038/s41388-021-01771-z Massagué, 2012, TGFβ signalling in context, Nat Rev Mol Cell Biol, 13, 616, 10.1038/nrm3434 Antsiferova, 2012, The bright and the dark sides of activin in wound healing and cancer, J Cell Sci, 125, 3929 Wiater, 2012, Roles of activin family in pancreatic development and homeostasis, Mol Cell Endocrinol, 359, 23, 10.1016/j.mce.2012.02.015 Zhao, 2020, Oncogene-induced senescence limits the progression of pancreatic neoplasia through production of activin A, Cancer Res, 80, 3359, 10.1158/0008-5472.CAN-19-3763 Qiu, 2016, Loss of activin receptor type 1B accelerates development of intraductal papillary mucinous neoplasms in mice with activated KRAS, Gastroenterology, 150, 218, 10.1053/j.gastro.2015.09.013 Ding, 2017, Activin A induces skeletal muscle catabolism via p38β mitogen-activated protein kinase, J Cachexia Sarcopenia Muscle, 8, 202, 10.1002/jcsm.12145 Paajanen, 2020, Elevated circulating activin A levels in patients with malignant pleural mesothelioma are related to cancer cachexia and reduced response to platinum-based chemotherapy, Clin Lung Cancer, 21, e142, 10.1016/j.cllc.2019.10.013 Nguyen, 2016, Tumor infiltrating lymphocytes and survival in patients with head and neck squamous cell carcinoma, Head Neck, 38, 1074, 10.1002/hed.24406 Paulsen, 2013, Coordinated regulation of synthesis and stability of RNA during the acute TNF-induced proinflammatory response, Proc Natl Acad Sci U S A, 110, 2240, 10.1073/pnas.1219192110 Bedi, 2020, Characterization of novel primary miRNA transcription units in human cells using Bru-seq nascent RNA sequencing, NAR Genom Bioinform, 2, lqz014, 10.1093/nargab/lqz014 Kirkconnell, 2017, Gene length as a biological timer to establish temporal transcriptional regulation, Cell Cycle, 16, 259, 10.1080/15384101.2016.1234550 Perusina Lanfranca, 2020, Interleukin 22 signaling regulates acinar cell plasticity to promote pancreatic tumor development in mice, Gastroenterology, 158, 1417, 10.1053/j.gastro.2019.12.010 Ettel, 2019, Expression and prognostic value of NSD1 and SETD2 in pancreatic ductal adenocarcinoma and its precursor lesions, Pathology, 51, 392, 10.1016/j.pathol.2019.02.005 Crowe, 2019, Semi-quantitative determination of protein expression using immunohistochemistry staining and analysis: an integrated protocol, Bio Protoc, 9, e3465, 10.21769/BioProtoc.3465 Young, 2019, The loss of ATRX increases susceptibility to pancreatic injury and oncogenic KRAS in female but not male mice, Cell Mol Gastroenterol Hepatol, 7, 93, 10.1016/j.jcmgh.2018.09.004 Wang, 2012, UTX regulates mesoderm differentiation of embryonic stem cells independent of H3K27 demethylase activity, Proc Natl Acad Sci U S A, 109, 15324, 10.1073/pnas.1204166109 Jackson, 2001, Analysis of lung tumor initiation and progression using conditional expression of oncogenic K-ras, Genes Dev, 15, 3243, 10.1101/gad.943001 Olive, 2004, Mutant p53 gain of function in two mouse models of Li-Fraumeni syndrome, Cell, 119, 847, 10.1016/j.cell.2004.11.004