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Inhibition of activin signaling in lung adenocarcinoma increases the therapeutic index of platinum chemotherapy
Marini, Kieren D.1,2; Croucher, David R.3,4,5; McCloy, Rachael A.3; Vaghjiani, Vijesh1; Gonzalez-Rajal, Alvaro3; Hastings, Jordan F.3; Chin, Venessa3; Szczepny, Anette1; Kostyrko, Kaja7; Marquez, Cesar7; Jayasekara, W. Samantha N.1; Alamgeer, Muhammad1,2,8; Boolell, Vishal1,8; Han, Jeremy Z. R.3; Waugh, Todd1; Lee, Hong Ching3; Oakes, Samantha R.3,4; Kumar, Beena9; Harrison, Craig A.1,2; Hedger, Mark P.1,2; Lorensuhewa, Nirmal10; Kita, Badia10; Barrow, Ross10; Robinson, Bruce W.11; de Kretser, David M.1,2,10; Wu, Jianmin4,12,13; Ganju, Vinod1,2; Sweet-Cordero, E. Alejandro7; Burgess, Andrew3,14; Martelotto, Luciano G.2,15; Rossello, Fernando J.16,17; Cain, Jason E.1; Watkins, D. Neil3,4,18
通讯作者Cain, Jason E.(1) ; Watkins, D. Neil(3,4,18)
刊名SCIENCE TRANSLATIONAL MEDICINE
2018-07-25
DOI10.1126/scitranslmed.aat3504
10期:451
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Cell Biology ; Medicine, Research & Experimental
研究领域[WOS]Cell Biology ; Research & Experimental Medicine
关键词[WOS]SQUAMOUS-CELL CARCINOMA ; TGF-BETA SUPERFAMILY ; DRUG-RESISTANCE ; CANCER ; EXPRESSION ; CISPLATIN ; CARBOPLATIN ; NEPHROTOXICITY ; INFLAMMATION ; FOLLISTATIN
英文摘要

Resistance to platinum chemotherapy is a long-standing problem in the management of lung adenocarcinoma. Using a whole-genome synthetic lethal RNA interference screen, we identified activin signaling as a critical mediator of innate platinum resistance. The transforming growth factor-beta (TGF beta) superfamily ligands activin A and growth differentiation factor 11 (GDF11) mediated resistance via their cognate receptors through TGF-beta-activated kinase 1 (TAK1), rather than through the SMAD family of transcription factors. Inhibition of activin receptor signaling or blockade of activin A and GDF11 by the endogenous protein follistatin overcame this resistance. Consistent with the role of activin signaling in acute renal injury, both therapeutic interventions attenuated acute cisplatin-induced nephrotoxicity, its major dose-limiting side effect. This cancer-specific enhancement of platinum-induced cell death has the potential to dramatically improve the safety and efficacy of chemotherapy in lung cancer patients.

语种英语
WOS记录号WOS:000440494200005
通讯作者邮箱jason.cain@hudson.org.au ; n.watkins@garvan.org.au
第一作者单位Hudson Inst Med Res, Melbourne, Vic 3168, Australia ; Monash Univ, Fac Med Nursing & Hlth Sci, Clayton, Vic 3800, Australia
通讯作者单位Hudson Inst Med Res, Melbourne, Vic 3168, Australia ; Garvan Inst Med Res, Kinghorn Canc Ctr, Darlinghurst, NSW 2010, Australia ; Univ New South Wales Sydney, St Vincents Clin Sch, Fac Med, Darlinghurst, NSW, Australia ; Monash Med Ctr, Dept Med Oncol, East Bentleigh, Vic 3165, Australia ; St Vincents Hosp, Dept Thorac Med, Darlinghurst, NSW 2010, Australia
ISSN1946-6234
引用统计
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/142594
专题北京大学临床肿瘤学院_生物样本库
作者单位1.Hudson Inst Med Res, Melbourne, Vic 3168, Australia;
2.Univ Coll Dublin, Sch Med, Dublin D04 V1W8, Ireland;
3.Monash Univ, Fac Med Nursing & Hlth Sci, Clayton, Vic 3800, Australia;
4.Garvan Inst Med Res, Kinghorn Canc Ctr, Darlinghurst, NSW 2010, Australia;
5.Univ New South Wales Sydney, St Vincents Clin Sch, Fac Med, Darlinghurst, NSW, Australia;
6.St Vincents Hosp, Dept Med Oncol, Darlinghurst, NSW 2010, Australia;
7.Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94158 USA;
8.Monash Med Ctr, Dept Med Oncol, East Bentleigh, Vic 3165, Australia;
9.Monash Med Ctr, Dept Pathol, Clayton, Vic 3168, Australia;
10.Paranta Biosci Ltd, Melbourne, Vic 3004, Australia;
11.Univ Western Australia, Queen Elizabeth II Med Ctr Unit, Sch Med & Pharmacol, Crawley, WA 6009, Australia;
12.Minist Educ, Key Lab Carcinogenesis & Translat Res, Beijing, Peoples R China;
13.Peking Univ, Canc Hosp & Inst, Ctr Canc Bioinformat, Beijing 100142, Peoples R China;
14.ANZAC Res Inst, Concord, NSW 2139, Australia;
15.Univ Melbourne, Ctr Canc Res, Fac Med Dent & Hlth Sci, Melbourne, Vic 3000, Australia;
16.Australian Regenerat Med Inst, Clayton, Vic 3800, Australia;
17.Monash Univ, Dept Anat & Dev Biol, Clayton, Vic 3800, Australia;
18.St Vincents Hosp, Dept Thorac Med, Darlinghurst, NSW 2010, Australia
推荐引用方式
GB/T 7714
Marini, Kieren D.,Croucher, David R.,McCloy, Rachael A.,et al. Inhibition of activin signaling in lung adenocarcinoma increases the therapeutic index of platinum chemotherapy[J]. SCIENCE TRANSLATIONAL MEDICINE,2018,10(451).
APA Marini, Kieren D..,Croucher, David R..,McCloy, Rachael A..,Vaghjiani, Vijesh.,Gonzalez-Rajal, Alvaro.,...&Watkins, D. Neil.(2018).Inhibition of activin signaling in lung adenocarcinoma increases the therapeutic index of platinum chemotherapy.SCIENCE TRANSLATIONAL MEDICINE,10(451).
MLA Marini, Kieren D.,et al."Inhibition of activin signaling in lung adenocarcinoma increases the therapeutic index of platinum chemotherapy".SCIENCE TRANSLATIONAL MEDICINE 10.451(2018).
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