Extracellular vesicle-packaged HIF-1α-stabilizing lncRNA from tumour-associated macrophages regulates aerobic glycolysis of breast cancer cells

被引：728

作者：

Chen, Fei ^{[1
,2
]}

Chen, Jianing ^{[1
,2
]}

Yang, Linbin ^{[1
,2
]}

Liu, Jiang ^{[1
,2
]}

Zhang, Xiaoqian ^{[1
,2
]}

Zhang, Yin ^{[1
]}

Tu, Qingqiang ^{[3
]}

Yin, Dong ^{[1
]}

Lin, Dechen ^{[1
]}

Wong, Ping-Pui ^{[1
]}

Huang, Di ^{[1
,2
]}

Xing, Yue ^{[1
,2
]}

Zhao, Jinghua ^{[1
,2
]}

Li, Mengfeng ^{[4
,5
]}

Liu, Qiang ^{[1
,2
]}

Su, Fengxi ^{[1
,2
]}

Su, Shicheng ^{[1
,2
]}

Song, Erwei ^{[1
,2
,6
]}

机构：

[1] Sun Yat Sen Univ, Sun Yat Sen Mem Hosp, Med Res Ctr, Guangdong Prov Key Lab Malignant Tumor Epigenet &, Guangzhou, Guangdong, Peoples R China

[2] Sun Yat Sen Univ, Sun Yat Sen Mem Hosp, Breast Tumor Ctr, Guangzhou, Guangdong, Peoples R China

[3] Sun Yat Sen Univ, Lab Anim Ctr, Guangzhou, Guangdong, Peoples R China

[4] Sun Yat Sen Univ, Key Lab Trop Dis Control, Minist Educ, Guangzhou, Guangdong, Peoples R China

[5] Sun Yat Sen Univ, Zhongshan Sch Med, Dept Microbiol, Guangzhou, Guangdong, Peoples R China

[6] Chinese Acad Sci, Guangzhou Inst Biomed & Hlth, Fountain Valley Inst Life Sci, Guangzhou, Guangdong, Peoples R China

来源：

NATURE CELL BIOLOGY | 2019年 / 21卷 / 04期

关键词：

METASTATIC NICHE FORMATION; GLUCOSE-METABOLISM; PROMOTE; GROWTH; INHIBITION; HYPOXIA; MICROENVIRONMENT; HETEROGENEITY; PROGRESSION; RESISTANCE;

D O I：

10.1038/s41556-019-0299-0

中图分类号：

Q2 [细胞生物学];

学科分类号：

071013 [干细胞生物学];

摘要：

Metabolic reprogramming is a hallmark of cancer. Here, we demonstrate that tumour-associated macrophages (TAMs) enhance the aerobic glycolysis and apoptotic resistance of breast cancer cells via the extracellular vesicle (EV) transmission of a myeloid-specific IncRNA, HIF-1 alpha-stabilizing long noncoding RNA (HISLA). Mechanistically, HISLA blocks the interaction of PHD2 and HIF-1 alpha to inhibit the hydroxylation and degradation of HIF-1 alpha. Reciprocally, lactate released from glycolytic tumour cells upregulates HISLA in macrophages, constituting a feed-forward loop between TAMs and tumour cells. Blocking EV-transmitted HISLA inhibits the glycolysis and chemoresistance of breast cancer in vivo. Clinically, HISLA expression in TAMs is associated with glycolysis, poor chemotherapeutic response and shorter survival of patients with breast cancer. Our study highlights the potential of IncRNAs as signal transducers that are transmitted between immune and tumour cells via EVs to promote cancer aerobic glycolysis.

引用

页码：498 / +

页数：16

共 51 条

[1]

The inflammatory micro-environment in tumor progression: The role of tumor-associated macrophages [J].

Allavena, Paola ;

Sica, Antonio ;

Solinas, Graziella ;

Porta, Chiara ;

Mantovani, Alberto .

CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY, 2008, 66 (01) :1-9

[2]

The mucin MUC1 modulates the tumor immunological microenvironment through engagement of the lectin Siglec-9 [J].

Beatson, Richard ;

Tajadura-Ortega, Virginia ;

Achkova, Daniela ;

Picco, Gianfranco ;

Tsourouktsoglou, Theodora-Dorita ;

Klausing, Sandra ;

Hillier, Matthew ;

Maher, John ;

Noll, Thomas ;

Crocker, Paul R. ;

Taylor-Papadimitriou, Joyce ;

Burchell, Joy M. .

NATURE IMMUNOLOGY, 2016, 17 (11) :1273-1281

[3]

Exosome Transfer from Stromal to Breast Cancer Cells Regulates Therapy Resistance Pathways [J].

Boelens, Mirjam C. ;

Wu, Tony J. ;

Nabet, Barzin Y. ;

Xu, Bihui ;

Qiu, Yu ;

Yoon, Taewon ;

Azzam, Diana J. ;

Victor, Christina Twyman-Saint ;

Wiemann, Brianne Z. ;

Ishwaran, Hemant ;

ter Brugge, Petra J. ;

Jonkers, Jos ;

Slingerland, Joyce ;

Minn, Andy J. .

CELL, 2014, 159 (03) :499-513

[4]

Paracrine Induction of HIF by Glutamate in Breast Cancer: EglN1 Senses Cysteine [J].

Briggs, Kimberly J. ;

Koivunen, Peppi ;

Cao, Shugeng ;

Backus, Keriann M. ;

Olenchock, Benjamin A. ;

Patel, Hetalben ;

Zhang, Qing ;

Signoretti, Sabina ;

Gerfen, Gary J. ;

Richardson, Andrea L. ;

Witkiewicz, Agnieszka K. ;

Cravatt, Benjamin F. ;

Clardy, Jon ;

Kaelin, William G., Jr. .

CELL, 2016, 166 (01) :126-139

[5]

CCL18 from Tumor-Associated Macrophages Promotes Breast Cancer Metastasis via PITPNM3 [J].

Chen, Jingqi ;

Yao, Yandan ;

Gong, Chang ;

Yu, Fengyan ;

Su, Shicheng ;

Chen, Jianing ;

Liu, Bodu ;

Deng, Hui ;

Wang, Fengsong ;

Lin, Ling ;

Yao, Herui ;

Su, Fengxi ;

Anderson, Karen S. ;

Liu, Qiang ;

Ewen, Mark E. ;

Yao, Xuebiao ;

Song, Erwei .

CANCER CELL, 2011, 19 (04) :541-555

[6]

Gpr132 sensing of lactate mediates tumor-macrophage interplay to promote breast cancer metastasis [J].

Chen, Peiwen ;

Zuo, Hao ;

Xiong, Hu ;

Kolar, Matthew J. ;

Chu, Qian ;

Saghatelian, Alan ;

Siegwart, Daniel J. ;

Wan, Yihong .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2017, 114 (03) :580-585

[7]

Functional polarization of tumour-associated macrophages by tumour-derived lactic acid [J].

Colegio, Oscar R. ;

Ngoc-Quynh Chu ;

Szabo, Alison L. ;

Chu, Thach ;

Rhebergen, Anne Marie ;

Jairam, Vikram ;

Cyrus, Nika ;

Brokowski, Carolyn E. ;

Eisenbarth, Stephanie C. ;

Phillips, Gillian M. ;

Cline, Gary W. ;

Phillips, Andrew J. ;

Medzhitov, Ruslan .

NATURE, 2014, 513 (7519) :559-+

[8]

Pancreatic cancer exosomes initiate pre-metastatic niche formation in the liver [J].

Costa-Silva, Bruno ;

Aiello, Nicole M. ;

Ocean, Allyson J. ;

Singh, Swarnima ;

Zhang, Haiying ;

Thakur, Basant Kumar ;

Becker, Annette ;

Hoshino, Ayuko ;

Mark, Milica Tesic ;

Molina, Henrik ;

Xiang, Jenny ;

Zhang, Tuo ;

Theilen, Till-Martin ;

Garcia-Santos, Guillermo ;

Williams, Caitlin ;

Ararso, Yonathan ;

Huang, Yujie ;

Rodrigues, Goncalo ;

Shen, Tang-Long ;

Labori, Knut Jorgen ;

Lothe, Inger Marie Bowitz ;

Kure, Elm H. ;

Hernandez, Jonathan ;

Doussot, Alexandre ;

Ebbesen, Saya H. ;

Grandgenett, Paul M. ;

Hollingsworth, Michael A. ;

Jain, Maneesh ;

Mallya, Kavita ;

Batra, Surinder K. ;

Jarnagin, William R. ;

Schwartz, Robert E. ;

Matei, Irina ;

Peinado, Hector ;

Stanger, Ben Z. ;

Bromberg, Jacqueline ;

Lyden, David .

NATURE CELL BIOLOGY, 2015, 17 (06) :816-+

[9]

The biology of cancer: Metabolic reprogramming fuels cell growth and proliferation [J].

DeBerardinis, Ralph J. ;

Lum, Julian J. ;

Hatzivassiliou, Georgia ;

Thompson, Craig B. .

CELL METABOLISM, 2008, 7 (01) :11-20

[10]

Fundamentals of cancer metabolism [J].

DeBerardinis, Ralph J. ;

Chandel, Navdeep S. .

SCIENCE ADVANCES, 2016, 2 (05)

← 1 2 3 4 5 6 →