Epithelial memory of inflammation limits tissue damage while promoting pancreatic tumorigenesis

被引：127

作者：

Del Poggetto, Edoardo ^{[1
,16
]}

Ho, I-Lin ^{[1
,2
]}

Balestrieri, Chiara ^{[3
,4
]}

Yen, Er-Yen ^{[1
,2
]}

Zhang, Shaojun ^{[1
,17
]}

Citron, Francesca ^{[1
]}

Shah, Rutvi ^{[1
,2
]}

Corti, Denise ^{[1
,18
]}

Diaferia, Giuseppe R. ^{[5
]}

Li, Chieh-Yuan ^{[1
,2
,19
]}

Loponte, Sara ^{[1
]}

Carbone, Federica ^{[1
,20
]}

Hayakawa, Yoku ^{[6
]}

Valenti, Giovanni ^{[6
]}

Jiang, Shan ^{[1
]}

Sapio, Luigi ^{[1
,21
]}

Jiang, Hong ^{[1
]}

Dey, Prasenjit ^{[7
,22
]}

Gao, Sisi ^{[1
]}

Deem, Angela K. ^{[1
]}

Rose-John, Stefan ^{[8
]}

Yao, Wantong ^{[9
]}

Ying, Haoqiang ^{[10
]}

Rhim, Andrew D. ^{[11
]}

Genovese, Giannicola ^{[12
]}

Heffernan, Timothy P. ^{[13
]}

Maitra, Anirban ^{[14
]}

Wang, Timothy C. ^{[6
]}

Wang, Linghua ^{[1
]}

Draetta, Giulio F. ^{[1
]}

Carugo, Alessandro ^{[13
]}

Natoli, Gioacchino ^{[5
,15
]}

Viale, Andrea ^{[1
]}

机构：

[1] Univ Texas MD Anderson Canc Ctr, Dept Genom Med, Houston, TX 77030 USA

[2] MD Anderson UTHlth Grad Sch Biomed Sci, Houston, TX 77030 USA

[3] San Raffaele Res Hosp, Expt Hematol Unit, I-20132 Milan, Italy

[4] IRCCS San Raffaele Sci Inst, Ctr Omics Sci, I-20132 Milan, Italy

[5] European Inst Oncol IRCCS, Dept Expt Oncol, I-20139 Milan, Italy

[6] Columbia Univ, Dept Digest & Liver Dis, Med Ctr, New York, NY 10032 USA

[7] Univ Texas MD Anderson Canc Ctr, Dept Canc Biol, Houston, TX 77030 USA

[8] Christian Albrechts Univ Kiel, Dept Biochem, D-24098 Kiel, Germany

[9] Univ Texas MD Anderson Canc Ctr, Dept Translat Mol Pathol, Houston, TX 77030 USA

[10] Univ Texas MD Anderson Canc Ctr, Dept Mol & Cellular Oncol, Houston, TX 77030 USA

[11] Univ Texas MD Anderson Canc Ctr, Dept Gastroenterol Hepatol & Nutr, Houston, TX 77030 USA

[12] Univ Texas MD Anderson Canc Ctr, Dept Genitourinary Med Oncol, Houston, TX 77030 USA

[13] Univ Texas MD Anderson Canc Ctr, TRACTION, Houston, TX 77030 USA

[14] Univ Texas MD Anderson Canc Ctr, Sheikh Ahmed Ctr Pancreat Canc Res, Houston, TX 77030 USA

[15] Humanitas Univ, I-20089 Milan, Italy

[16] AXXAM, I-20091 Milan, Italy

[17] Guangdong Acad Med Sci, Med Res Ctr, Guangdong Prov Peoples Hosp, Guangzhou 510080, Peoples R China

[18] F Hoffrrann La Roche Ltd, CH-4070 Basel, Switzerland

[19] Mission Bio, San Francisco, CA 94080 USA

[20] Nerviano Med Sci, I-20014 Nervier, Italy

[21] Univ Campania Luigi Vanvitelli, Dept Precis Med, I-80138 Naples, Italy

[22] Roswell Pk Comprehens Canc Ctr, Dept Immunol, Buffalo, NY 14263 USA

来源：

SCIENCE | 2021年 / 373卷 / 6561期

基金：

欧盟地平线“2020”;

关键词：

TO-DUCTAL METAPLASIA; DIFFERENTIAL EXPRESSION ANALYSIS; NF-KAPPA-B; ONCOGENIC KRAS; STEM-CELLS; INTRAEPITHELIAL NEOPLASIA; ACINAR; CANCER; ACTIVATION; GROWTH;

D O I：

10.1126/science.abj0486

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Inflammation is a major risk factor for pancreatic ductal adenocarcinoma (PDAC). When occurring in the context of pancreatitis, KRAS mutations accelerate tumor development in mouse models. We report that long after its complete resolution, a transient inflammatory event primes pancreatic epithelial cells to subsequent transformation by oncogenic KRAS. Upon recovery from acute inflammation, pancreatic epithelial cells display an enduring adaptive response associated with sustained transcriptional and epigenetic reprogramming. Such adaptation enables the reactivation of acinar-to-ductal metaplasia (ADM) upon subsequent inflammatory events, thereby limiting tissue damage through a rapid decrease of zymogen production. We propose that because activating mutations of KRAS maintain an irreversible ADM, they may be beneficial and under strong positive selection in the context of recurrent pancreatitis.

引用

页码：1326 / +

页数：45

共 87 条

[1] Pancreatic duct epithelial cell-isolation and cultivation in two-dimensional and three-dimensional culture systems
Agbunag, Cristina
Lee, Kyoung Eun
Buontempo, Serena
Bar-Sagi, Dafna
[J]. REGULATORS AND EFFECTORS OF SMALL GTPASES: RAS FAMILY, 2006, 407 : 703 - 710
[2] A gene-environment-induced epigenetic program initiates tumorigenesis
Alonso-Curbelo, Direna
Ho, Yu-Jui
Burdziak, Cassandra
Maag, Jesper L. V.
Morris, John P.
Chandwani, Rohit
Chen, Hsuan-An
Tsanov, Kaloyan M.
Barriga, Francisco M.
Luan, Wei
Tasdemir, Nilgun
Livshits, Geulah
Azizi, Elham
Chun, Jaeyoung
Wilkinson, John E.
Mazutis, Linas
Leach, Steven D.
Koche, Richard
Pe'er, Dana
Lowe, Scott W.
[J]. NATURE, 2021, 590 (7847) : 642 - 648
[3] An atlas of active enhancers across human cell types and tissues
Andersson, Robin
Gebhard, Claudia
Miguel-Escalada, Irene
Hoof, Ilka
Bornholdt, Jette
Boyd, Mette
Chen, Yun
Zhao, Xiaobei
Schmidl, Christian
Suzuki, Takahiro
Ntini, Evgenia
Arner, Erik
Valen, Eivind
Li, Kang
Schwarzfischer, Lucia
Glatz, Dagmar
Raithel, Johanna
Lilje, Berit
Rapin, Nicolas
Bagger, Frederik Otzen
Jorgensen, Mette
Andersen, Peter Refsing
Bertin, Nicolas
Rackham, Owen
Burroughs, A. Maxwell
Baillie, J. Kenneth
Ishizu, Yuri
Shimizu, Yuri
Furuhata, Erina
Maeda, Shiori
Negishi, Yutaka
Mungall, Christopher J.
Meehan, Terrence F.
Lassmann, Timo
Itoh, Masayoshi
Kawaji, Hideya
Kondo, Naoto
Kawai, Jun
Lennartsson, Andreas
Daub, Carsten O.
Heutink, Peter
Hume, David A.
Jensen, Torben Heick
Suzuki, Harukazu
Hayashizaki, Yoshihide
Mueller, Ferenc
Forrest, Alistair R. R.
Carninci, Piero
Rehli, Michael
Sandelin, Albin
[J]. NATURE, 2014, 507 (7493) : 455 - +
[4] p53 mutations cooperate with oncogenic Kras to promote adenocarcinoma from pancreatic ductal cells
Bailey, J. M.
Hendley, A. M.
Lafaro, K. J.
Pruski, M. A.
Jones, N. C.
Alsina, J.
Younes, M.
Maitra, A.
McAllister, F.
Iacobuzio-Donahue, C. A.
Leach, S. D.
[J]. ONCOGENE, 2016, 35 (32) : 4282 - 4288
[5] DCLK1 Marks a Morphologically Distinct Subpopulation of Cells With Stem Cell Properties in Preinvasive Pancreatic Cancer
Bailey, Jennifer M.
Alsina, Janivette
Rasheed, Zeshaan A.
McAllister, Florencia M.
Fu, Ya-Yuan
Plentz, Ruben
Zhang, Hao
Pasricha, Pankaj J.
Bardeesy, Nabeel
Matsui, William
Maitra, Anirban
Leach, Steven D.
[J]. GASTROENTEROLOGY, 2014, 146 (01) : 245 - 256
[6] MEME SUITE: tools for motif discovery and searching
Bailey, Timothy L.
Boden, Mikael
Buske, Fabian A.
Frith, Martin
Grant, Charles E.
Clementi, Luca
Ren, Jingyuan
Li, Wilfred W.
Noble, William S.
[J]. NUCLEIC ACIDS RESEARCH, 2009, 37 : W202 - W208
[7] Co-optation of Tandem DNA Repeats for the Maintenance of Mesenchymal Identity
Balestrieri, Chiara
Alfarano, Gabriele
Milan, Marta
Tosi, Valentina
Prosperini, Elena
Nicoli, Paola
Palamidessi, Andrea
Scita, Giorgio
Diaferia, Giuseppe R.
Natoli, Gioacchino
[J]. CELL, 2018, 173 (05) : 1150 - +
[8] Bowie J. H., 2013, HDB BIOL ACTIVE PEPT, V2, P338
[9] Buenrostro Jason D, 2015, Curr Protoc Mol Biol, V109, DOI 10.1002/0471142727.mb2129s109
[10] Buenrostro JD, 2013, NAT METHODS, V10, P1213, DOI [10.1038/NMETH.2688, 10.1038/nmeth.2688]

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