Tumor-stromal IL1β/ NFκB / ESE3 Signal Axis Drives Pancreatic Cancer Fibrosis, Chemoresistance, Prognosis
作者： Tiansuo Zhao , Di Xiao , Fanjie Jin , Hongwei Wang , Jing Liu
DOI: 10.1101/2020.07.27.222455
关键词:
摘要: Pancreatic stellate cells (PSCs) play a pivotal role in pancreatic fibrosis and ductal adenocarcinoma (PDAC) progression. The mechanisms controlling PSC activation is not completely understood. Here we investigated the of ESE3 (Epithelium-Specific ETS factor 3) activation. We discovered that PDAC patients expression was increased while decreased tumor cells. overexpression promoted Condition medium from ESE3-overexprssing promotes cell migration, chemoresistance, growth fibrosis. directly induced transcription -SMA, Collagen 1 IL-1{beta} by binding to sites on their promoters activate PSC. On other hand, upregulates through NF{kappa}B required for derived IL-1{beta}. Clinical data showed upregulation positively correlated with size, pTNM stage, CA19-9, CEA CA242 level serum. an independent negative prognostic disease-free survival overall among patients. Inhibition IL-1{beta}/ (PSC)/ positive feedback loop represents promising therapeutic strategy reduce increase chemotherapeutic efficacy PDAC.
sci-hub.st 参考文章(35)
Susumu Yamazaki, Nobuhiro Nakano, Asuka Honjo, Mutsuko Hara, Keiko Maeda, Chiharu Nishiyama, Jiro Kitaura, Yoshikazu Ohtsuka, Ko Okumura, Hideoki Ogawa, Toshiaki Shimizu, The Transcription Factor Ehf Is Involved in TGF-β–Induced Suppression of FcεRI and c-Kit Expression and FcεRI-Mediated Activation in Mast Cells Journal of Immunology. ,vol. 195, pp. 3427- 3435 ,(2015) , 10.4049/JIMMUNOL.1402856
Silke Appel, Anita Bringmann, Frank Grünebach, Markus M. Weck, Jürgen Bauer, Peter Brossart, Epithelial-specific transcription factor ESE-3 is involved in the development of monocyte-derived DCs. Blood. ,vol. 107, pp. 3265- 3270 ,(2006) , 10.1182/BLOOD-2005-06-2480
M Sinn, C Denkert, J K Striefler, U Pelzer, J M Stieler, M Bahra, P Lohneis, B Dörken, H Oettle, H Riess, B V Sinn, α-Smooth muscle actin expression and desmoplastic stromal reaction in pancreatic cancer: results from the CONKO-001 study British Journal of Cancer. ,vol. 111, pp. 1917- 1923 ,(2014) , 10.1038/BJC.2014.495
R Jaster, G Sparmann, J Emmrich, S Liebe, Extracellular signal regulated kinases are key mediators of mitogenic signals in rat pancreatic stellate cells Gut. ,vol. 51, pp. 579- 584 ,(2002) , 10.1136/GUT.51.4.579
Ralf Jesnowski, Daniel Fürst, Jörg Ringel, Ying Chen, Andrea Schrödel, Jörg Kleeff, Armin Kolb, Wolfgang D Schareck, Matthias Löhr, Immortalization of pancreatic stellate cells as an in vitro model of pancreatic fibrosis: deactivation is induced by matrigel and N-acetylcysteine. Laboratory Investigation. ,vol. 85, pp. 1276- 1291 ,(2005) , 10.1038/LABINVEST.3700329
Eric S Silverman, Rebecca M Baron, Lyle J Palmer, Louis Le, Arlene Hallock, Venkat Subramaniam, Richard J Riese, Matthew D McKenna, Xuesong Gu, Towia A Libermann, Antonio Tugores, Kathleen J Haley, Stephanie Shore, Jeffrey M Drazen, Scott T Weiss, None, Constitutive and cytokine-induced expression of the ETS transcription factor ESE-3 in the lung American Journal of Respiratory Cell and Molecular Biology. ,vol. 27, pp. 697- 704 ,(2002) , 10.1165/RCMB.2002-0011OC
Koen Kas, Eduardo Finger, Franck Grall, Xuesong Gu, Yasmin Akbarali, Jay Boltax, Avi Weiss, Peter Oettgen, Rosana Kapeller, Towia A. Libermann, ESE-3, a novel member of an epithelium-specific ets transcription factor subfamily, demonstrates different target gene specificity from ESE-1. Journal of Biological Chemistry. ,vol. 275, pp. 2986- 2998 ,(2000) , 10.1074/JBC.275.4.2986
Victor I Sementchenko, Dennis K Watson, Ets target genes: past, present and future Oncogene. ,vol. 19, pp. 6533- 6548 ,(2000) , 10.1038/SJ.ONC.1204034
Huan Xie, Xiaomei Bian, Amit Anil Deorukhkar, Sunil Krishnan, Abstract 2889: Development of a novel nanoconstruct for tumor hypoxia photothermal therapy Cancer Research. ,vol. 72, pp. 2889- 2889 ,(2012) , 10.1158/1538-7445.AM2012-2889
S Mitsunaga, M Ikeda, S Shimizu, I Ohno, J Furuse, M Inagaki, S Higashi, H Kato, K Terao, A Ochiai, Serum levels of IL-6 and IL-1β can predict the efficacy of gemcitabine in patients with advanced pancreatic cancer. British Journal of Cancer. ,vol. 108, pp. 2063- 2069 ,(2013) , 10.1038/BJC.2013.174