Wei Zhou, Wei Sun, Mingo M H Yung, Sheng Dai, Yihua Cai, Chi-Wei Chen, Yunxiao Meng, Jennifer B Lee, John C Braisted, Yinghua Xu, Noel T Southall, Paul Shinn, Xuefeng Huang, Zhangfa Song, Xiulei Chen, Yan Kai, Xin Cai, Zongzhu Li, Qiang Hao, Annie N Y Cheung, Hextan Y S Ngan, Stephanie S Liu, Stephanie Barak, Jing Hao, Zhijun Dai, Alexandros Tzatsos, Weiqun Peng, Huadong Pei, Zhiyong Han, David W Chan, Wei Zheng, Wenge Zhu
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...
April 17, 2018: Oncogene