Cancer Cell-Autonomous TRAIL-R Signaling Promotes KRAS-Driven Cancer Progression, Invasion, and Metastasis

被引：157

作者：

von Karstedt, Silvia ^{[1
]}

Conti, Annalisa ^{[1
,2
]}

Nobis, Max ^{[3
]}

Montinaro, Antonella ^{[1
]}

Hartwig, Torsten ^{[1
]}

Lemke, Johannes ^{[1
]}

Legler, Karen ^{[4
]}

Annewanter, Franka ^{[4
]}

Campbell, Andrew D. ^{[3
]}

Taraborrelli, Lucia ^{[1
]}

Grosse-Wilde, Anne ^{[5
,6
]}

Coy, Johannes F. ^{[5
,7
]}

El-Bahrawy, Mona A. ^{[8
]}

Bergmann, Frank ^{[9
]}

Koschny, Ronald ^{[10
]}

Werner, Jens ^{[11
]}

Ganten, Tom M. ^{[10
]}

Schweiger, Thomas ^{[12
,13
]}

Hoetzenecker, Konrad ^{[13
]}

Kenessey, Istvan ^{[14
]}

Hegedues, Balazs ^{[12
,15
]}

Bergmann, Michael ^{[12
]}

Hauser, Charlotte ^{[16
]}

Egberts, Jan-Hendrik ^{[16
]}

Becker, Thomas ^{[16
]}

Roecken, Christoph ^{[17
]}

Kalthoff, Holger ^{[4
]}

Trauzold, Anna ^{[4
,16
]}

Anderson, Kurt I. ^{[3
]}

Sansom, Owen J. ^{[3
]}

Walczak, Henning ^{[1
]}

机构：

[1] UCL, UCL Canc Inst, Ctr Cell Death Canc & Inflammat, London WC1E 6DD, England

[2] Fdn IRCCS Ist Nazl Tumori, Dept Expt Oncol & Mol Med, I-20133 Milan, Italy

[3] Beatson Inst Canc Res, Glasgow G61 1BD, Lanark, Scotland

[4] Univ Kiel, Inst Expt Canc Res, Div Mol Oncol, D-24105 Kiel, Germany

[5] German Canc Res Ctr, D-69120 Heidelberg, Germany

[6] Inst Syst Biol, Seattle, WA 98109 USA

[7] TAVARLIN AG, D-64319 Pfungstadt, Germany

[8] Univ London Imperial Coll Sci Technol & Med, Dept Histopathol, London W12 0NN, England

[9] Univ Heidelberg Hosp, Inst Pathol, D-69120 Heidelberg, Germany

[10] Univ Heidelberg Hosp, Dept Gastroenterol, D-69120 Heidelberg, Germany

[11] Univ Heidelberg Hosp, Dept Surg, D-69120 Heidelberg, Germany

[12] Med Univ Vienna, Dept Thorac Surg, A-1090 Vienna, Austria

[13] Med Univ Vienna, Christian Doppler Lab Cardiac & Thorac Diag & Reg, A-1090 Vienna, Austria

[14] Semmelweis Univ Budapest, Dept Pathol 2, H-1091 Budapest, Hungary

[15] Semmelweis Univ, Hungarian Acad Sci, Mol Oncol Res Grp, H-1091 Budapest, Hungary

[16] Univ Hosp Schleswig Holstein, Dept Gen Surg Visceral Thorac Transplantat & Pedi, D-24105 Kiel, Germany

[17] Univ Kiel, Dept Pathol, D-24105 Kiel, Germany

来源：

CANCER CELL | 2015年 / 27卷 / 04期

基金：

英国惠康基金; 欧洲研究理事会;

关键词：

NF-KAPPA-B; LUNG-CANCER; TUMOR INITIATION; INDUCED SURVIVAL; DEATH RECEPTORS; RAC ACTIVITY; MOUSE MODEL; K-RAS; APOPTOSIS; ACTIVATION;

D O I：

10.1016/j.ccell.2015.02.014

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Many cancers harbor oncogenic mutations of KRAS. Effectors mediating cancer progression, invasion, and metastasis in KRAS-mutated cancers are only incompletely understood. Here we identify cancer cell-expressed murine TRAIL-R, whose main function ascribed so far has been the induction of apoptosis as a crucial mediator of KRAS-driven cancer progression, invasion, and metastasis and in vivo Rac-1 activation. Cancer cell-restricted genetic ablation of murine TRAIL-R in autochthonous KRAS-driven models of non-small-cell lung cancer (NSCLC) and pancreatic ductal adenocarcinoma (PDAC) reduces tumor growth, blunts metastasis, and prolongs survival by inhibiting cancer cell-autonomous migration, proliferation, and invasion. Consistent with this, high TRAIL-R2 expression correlates with invasion of human PDAC into lymph vessels and with shortened metastasis-free survival of KRAS-mutated colorectal cancer patients.

引用

页码：561 / 573

页数：13

共 67 条

[1] Mutational spectra of PTEN/MMAC1 gene: a tumor suppressor with lipid phosphatase activity [J].

Ali, IU ;

Schriml, LM ;

Dean, M .

JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE, 1999, 91 (22) :1922-1932

[2] Visualization of small GTPase activity with fluorescence resonance energy transfer-based biosensors [J].

Aoki, Kazuhiro ;

Matsuda, Michiyuki .

NATURE PROTOCOLS, 2009, 4 (11) :1623-1631

[3] Safety and antitumor activity of recombinant soluble Apo2 ligand [J].

Ashkenazi, A ;

Pai, RC ;

Fong, S ;

Leung, S ;

Lawrence, DA ;

Masters, SA ;

Blackie, C ;

Chang, L ;

McMurtrey, AE ;

Hebert, A ;

DeForge, L ;

Koumenis, IL ;

Lewis, D ;

Harris, L ;

Bussiere, J ;

Koeppen, H ;

Shahrokh, Z ;

Schwall, RH .

JOURNAL OF CLINICAL INVESTIGATION, 1999, 104 (02) :155-162

[4] Kinome profiling of non-canonical TRAIL signaling reveals RIP1-Src-STAT3-dependent invasion in resistant non-small cell lung cancer cells [J].

Azijli, Kaamar ;

Yuvaraj, Saravanan ;

Peppelenbosch, Maikel P. ;

Wurdinger, Thomas ;

Dekker, Henk ;

Joore, Jos ;

van Dijk, Evert ;

Quax, Wim J. ;

Peters, Godefridus J. ;

de Jong, Steven ;

Kruyt, Frank A. E. .

JOURNAL OF CELL SCIENCE, 2012, 125 (19) :4651-4661

[5]

Baines AT, 2011, FUTURE MED CHEM, V3, P1787, DOI [10.4155/FMC.11.121, 10.4155/fmc.11.121]

[6] ACTIVATION OF THE MOUSE CELLULAR HARVEY-RAS GENE IN CHEMICALLY-INDUCED BENIGN SKIN PAPILLOMAS [J].

BALMAIN, A ;

RAMSDEN, M ;

BOWDEN, GT ;

SMITH, J .

NATURE, 1984, 307 (5952) :658-660

[7] TRAIL-induced survival and proliferation of SCLC cells is mediated by ERK and dependent on TRAIL-R2/DR5 expression in the absence of caspase-8 [J].

Belyanskaya, Larisa L. ;

Ziogas, Algirdas ;

Ns-Donaldson, Sally Hopki ;

Kurtz, Stefanie ;

Simon, Hans-Uwe ;

Stahel, Rolf ;

Zangemeister-Wittke, Uwe .

LUNG CANCER, 2008, 60 (03) :355-365

[8]

BOS JL, 1989, CANCER RES, V49, P4682

[9] Requirement for Interaction of PI3-Kinase p110α with RAS in Lung Tumor Maintenance [J].

Castellano, Esther ;

Sheridan, Clare ;

Thin, May Zaw ;

Nye, Emma ;

Spencer-Dene, Bradley ;

Diefenbacher, Markus E. ;

Moore, Christopher ;

Kumar, Madhu S. ;

Murillo, Miguel M. ;

Groenroos, Eva ;

Lassailly, Francois ;

Stamp, Gordon ;

Downward, Julian .

CANCER CELL, 2013, 24 (05) :617-630

[10] Increased susceptibility to tumor initiation and metastasis in TNF-related apoptosis-inducing ligand-deficient mice [J].

Cretney, E ;

Takeda, K ;

Yagita, H ;

Glaccum, M ;

Peschon, JJ ;

Smyth, MJ .

JOURNAL OF IMMUNOLOGY, 2002, 168 (03) :1356-1361

← 1 2 3 4 5 6 7 →