Nature Communications (Oct 2018)
Targeting SPINK1 in the damaged tumour microenvironment alleviates therapeutic resistance
- Fei Chen,
- Qilai Long,
- Da Fu,
- Dexiang Zhu,
- Yan Ji,
- Liu Han,
- Boyi Zhang,
- Qixia Xu,
- Bingjie Liu,
- Yan Li,
- Shanshan Wu,
- Chen Yang,
- Min Qian,
- Jianmin Xu,
- Suling Liu,
- Liu Cao,
- Y. Eugene Chin,
- Eric W.-F. Lam,
- Jean-Philippe Coppé,
- Yu Sun
Affiliations
- Fei Chen
- Key Laboratory of Tissue Microenvironment and Tumour, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences
- Qilai Long
- Department of Urology, Zhongshan Hospital, Fudan University
- Da Fu
- Central Laboratory for Medical Research, Shanghai Tenth People’s Hospital, Tongji University School of Medicine
- Dexiang Zhu
- Department of General Surgery, Zhongshan Hospital, Fudan University
- Yan Ji
- Key Laboratory of Tissue Microenvironment and Tumour, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences
- Liu Han
- Key Laboratory of Tissue Microenvironment and Tumour, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences
- Boyi Zhang
- Key Laboratory of Tissue Microenvironment and Tumour, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences
- Qixia Xu
- Institute of Health Sciences, Shanghai Jiao Tong University School of Medicine & Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences
- Bingjie Liu
- Fudan University Shanghai Cancer Center & Institutes of Biomedical Sciences, Shanghai Medical College, Key Laboratory of Breast Cancer in Shanghai, Innovation Center for Cell Signaling Network, Cancer Institutes, Fudan University
- Yan Li
- Key Laboratory of Tissue Microenvironment and Tumour, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences
- Shanshan Wu
- Key Laboratory of Tissue Microenvironment and Tumour, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences
- Chen Yang
- Key Laboratory of Tissue Microenvironment and Tumour, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences
- Min Qian
- Key Laboratory of Tissue Microenvironment and Tumour, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences
- Jianmin Xu
- Department of General Surgery, Zhongshan Hospital, Fudan University
- Suling Liu
- Fudan University Shanghai Cancer Center & Institutes of Biomedical Sciences, Shanghai Medical College, Key Laboratory of Breast Cancer in Shanghai, Innovation Center for Cell Signaling Network, Cancer Institutes, Fudan University
- Liu Cao
- Key Laboratory of Medical Cell Biology, China Medical University
- Y. Eugene Chin
- Institute of Biology and Medical Sciences, Soochow University Medical College
- Eric W.-F. Lam
- Department of Surgery and Cancer, Imperial College London
- Jean-Philippe Coppé
- Department of Laboratory Medicine, Helen Diller Family Comprehensive Cancer Center, University of California
- Yu Sun
- Key Laboratory of Tissue Microenvironment and Tumour, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences
- DOI
- https://doi.org/10.1038/s41467-018-06860-4
- Journal volume & issue
-
Vol. 9,
no. 1
pp. 1 – 19
Abstract
Tumour microenvironment actively contributes to drug resistance in clinical oncology. Here, the authors show that genotoxic stress induces senescence in human stromal cells, which in turn secrete serine protease inhibitor Kazal type 1 (SPINK1) and promote acquired resistance of cancer cells via EGFR-mediated paracrine signaling.
