Targeting SPINK1 in the damaged tumour microenvironment alleviates therapeutic resistance
文献类型：期刊论文
| 作者 | Chen, Fei2; Ji, Yan2; Han, Liu2; Zhang, Boyi2; Li, Yan2; Wu, Shanshan2; Yang, Chen2; Qian, Min2; Sun, Yu2,6,7; Long, Qilai3 |
| 刊名 | NATURE COMMUNICATIONS
 |
| 出版日期 | 2018 |
| 卷号 | 9期号:-页码:4315 |
| ISSN号 | 2041-1723 |
| DOI | 10.1038/s41467-018-06860-4 |
| 文献子类 | Article |
| 英文摘要 | Chemotherapy and radiation not only trigger cancer cell apoptosis but also damage stromal cells in the tumour microenvironment (TME), inducing a senescence-associated secretory phenotype (SASP) characterized by chronic secretion of diverse soluble factors. Here we report serine protease inhibitor Kazal type I (SPINK1), a SASP factor produced in human stromal cells after genotoxic treatment. DNA damage causes SPINK1 expression by engaging NF-kappa B and C/EBP, while paracrine SPINK1 promotes cancer cell aggressiveness particularly chemoresistance. Strikingly, SPINK1 reprograms the expression profile of cancer cells, causing prominent epithelial-endothelial transition (EET), a phenotypic switch mediated by EGFR signaling but hitherto rarely reported for a SASP factor. In vivo, SPINK1 is expressed in the stroma of solid tumours and is routinely detectable in peripheral blood of cancer patients after chemotherapy. Our study substantiates SPINK1 as both a targetable SASP factor and a novel noninvasive biomarker of therapeutically damaged TME for disease control and clinical surveillance. |
| 学科主题 | Science & Technology - Other Topics |
| WOS关键词 | INFLAMMATORY CYTOKINE SECRETION ; EPITHELIAL-CELL LINE ; PROSTATE-CANCER ; TRYPSIN-INHIBITOR ; SENESCENCE ; METASTASIS ; EXPRESSION ; PHENOTYPE ; RECEPTOR ; NETWORK |
| 语种 | 英语 |
| WOS记录号 | WOS:000447509500003 |
| 出版者 | NATURE PUBLISHING GROUP |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.144/handle/331004/868]  |
| 专题 | 中国科学院上海生命科学研究院营养科学研究所 |
| 作者单位 | 1.Univ Washington, VAPSHCS, Dept Med, Seattle, WA 98195 USA, 2.Univ Chinese Acad Sci, Shanghai Inst Biol Sci, Chinese Acad Sci, Key Lab Tissue Microenvironm & Tumour, Shanghai 200031, Peoples R China; 3.Fudan Univ, Zhongshan Hosp, Dept Urol, Shanghai 200032, Peoples R China; 4.Tongji Univ, Shanghai Peoples Hosp 10, Cent Lab Med Res, Sch Med, Shanghai 200072, Peoples R China; 5.Fudan Univ, Zhongshan Hosp, Dept Gen Surg, Shanghai 200032, Peoples R China; 6.Shanghai Jiao Tong Univ, Sch Med, Inst Hlth Sci, Shanghai 200031, Peoples R China; 7.Chinese Acad Sci, Shanghai Inst Biol Sci, Shanghai 200031, Peoples R China; 8.Fudan Univ, Shanghai Canc Ctr, Shanghai 200032, Peoples R China; 9.Fudan Univ, Inst Biomed Sci, Shanghai Med Coll,Canc Inst, Key Lab Breast Canc Shanghai,Innovat Ctr Cell Sig, Shanghai 200032, Peoples R China; 10.China Med Univ, Key Lab Med Cell Biol, Shenyang 110122, Liaoning, Peoples R China; |
| 推荐引用方式 GB/T 7714 | Chen, Fei,Ji, Yan,Han, Liu,et al. Targeting SPINK1 in the damaged tumour microenvironment alleviates therapeutic resistance[J]. NATURE COMMUNICATIONS,2018,9(-):4315. |
| APA | Chen, Fei.,Ji, Yan.,Han, Liu.,Zhang, Boyi.,Li, Yan.,...&,.(2018).Targeting SPINK1 in the damaged tumour microenvironment alleviates therapeutic resistance.NATURE COMMUNICATIONS,9(-),4315. |
| MLA | Chen, Fei,et al."Targeting SPINK1 in the damaged tumour microenvironment alleviates therapeutic resistance".NATURE COMMUNICATIONS 9.-(2018):4315. |
入库方式： OAI收割
来源：上海营养与健康研究所
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