Autocrine activation of JAK2 by IL-11 promotes platinum drug resistance.
Autocrine activation of JAK2 by IL-11 promotes platinum drug resistance.
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IL-11自分泌激活JAK 2促进铂类药物耐药性。
DOI：
10.1038/s41388-018-0238-8
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发表时间：
2018-07
期刊：
影响因子：
8
通讯作者：
Zhu W
中科院分区：
文献类型：
--
作者：
Zhou W;Sun W;Yung MMH;Dai S;Cai Y;Chen CW;Meng Y;Lee JB;Braisted JC;Xu Y;Southall NT;Shinn P;Huang X;Song Z;Chen X;Kai Y;Cai X;Li Z;Hao Q;Cheung ANY;Ngan HYS;Liu SS;Barak S;Hao J;Dai Z;Tzatsos A;Peng W;Pei H;Han Z;Chan DW;Zheng W;Zhu W
Antineoplastic platinum agents are used in first-line treatment of ovarian cancer, but treatment failure frequently results from platinum drug resistance. Emerging observations suggest a role of reactive oxygen species (ROS) in the resistance of cancer drugs including platinum drugs. However, the molecular link between ROS and cellular survival pathway is poorly understood. Using quantitative high throughput combinational screen (qHTCS) and genomic sequencing, we show that in platinum resistant ovarian cancer elevated ROS levels sustain high level of IL-11 by stimulating FRA1-mediated IL-11 expression and increased IL-11 causes resistance to platinum drugs by constitutively activating JAK2-STAT5 via an autocrine mechanism. Inhibition of JAK2 by LY2784544 or IL-11 by anti-IL-11 antibody overcomes the platinum resistance in vitro or in vivo. Significantly, clinic studies also confirm the activated IL-11-JAK2 pathway in platinum-resistant ovarian cancer patients, which highly correlates with poor prognosis. These findings not only identify a novel ROS-IL-11-JAK2-mediated platinum resistance mechanism but also provide a new strategy for using LY2784544 or IL-11-mediated immunotherapy to treat platinum-resistant ovarian cancer.
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DOI：
10.1056/nejmoa065202
发表时间：
2007-02-01
期刊：
The New England journal of medicine
影响因子：
--
作者：
Scott LM;Tong W;Levine RL;Scott MA;Beer PA;Stratton MR;Futreal PA;Erber WN;McMullin MF;Harrison CN;Warren AJ;Gilliland DG;Lodish HF;Green AR
通讯作者：
Green AR
骨髓增生性肿瘤中的体细胞CALR突变与未突破的JAK2。
DOI：
10.1056/nejmoa1312542
发表时间：
2013-12-19
期刊：
The New England journal of medicine
影响因子：
--
作者：
Nangalia J;Massie CE;Baxter EJ;Nice FL;Gundem G;Wedge DC;Avezov E;Li J;Kollmann K;Kent DG;Aziz A;Godfrey AL;Hinton J;Martincorena I;Van Loo P;Jones AV;Guglielmelli P;Tarpey P;Harding HP;Fitzpatrick JD;Goudie CT;Ortmann CA;Loughran SJ;Raine K;Jones DR;Butler AP;Teague JW;O'Meara S;McLaren S;Bianchi M;Silber Y;Dimitropoulou D;Bloxham D;Mudie L;Maddison M;Robinson B;Keohane C;Maclean C;Hill K;Orchard K;Tauro S;Du MQ;Greaves M;Bowen D;Huntly BJP;Harrison CN;Cross NCP;Ron D;Vannucchi AM;Papaemmanuil E;Campbell PJ;Green AR
通讯作者：
Green AR
影响因子：
64.5
作者：
Parganas, E;Wang, D;Ihle, JN
通讯作者：
Ihle, JN
影响因子：
14.8
作者：
Olive, Peggy L.;Banath, Judit P.
通讯作者：
Banath, Judit P.
影响因子：
15.9
作者：
Bromberg, J
通讯作者：
Bromberg, J