Long Noncoding RNA LINC00092 Acts in Cancer-Associated Fibroblasts to Drive Glycolysis and Progression of Ovarian Cancer

被引：228

作者：

Zhao, Linjie ^{[1
,2
,3
]}

Ji, Gaili ^{[1
,2
,3
]}

Le, Xiaobing ^{[1
,2
,3
]}

Wang, Chenlu ^{[1
,2
,3
]}

Xu, Lian ^{[4
]}

Feng, Min ^{[4
]}

Zhang, Yaguang ^{[1
,2
,3
]}

Yang, Huiliang ^{[5
]}

Xuan, Yu ^{[1
,2
,3
]}

Yang, Yanfei ^{[1
,2
,3
]}

Lei, Lingzi ^{[1
,2
,3
]}

Yang, Qilian ^{[1
,2
,3
]}

Lau, Wayne Bond ^{[6
]}

Lau, Bonnie ^{[7
]}

Chen, Yi ^{[8
]}

Deng, Xiangbing ^{[8
]}

Yao, Shaohua ^{[1
,2
,3
]}

Yi, Tao ^{[1
,2
,3
]}

Zhao, Xia ^{[1
,2
,3
]}

Wei, Yuquan ^{[1
,2
,3
]}

Zhou, Shengtao ^{[1
,2
,3
]}

机构：

[1] Sichuan Univ, Dept Obstet & Gynecol, Key Lab Birth Defects & Related Dis, Chengdu, Peoples R China

[2] Sichuan Univ, West China Second Hosp, Children MOE & State Key Lab Biotherapy, Chengdu, Peoples R China

[3] Sichuan Univ, Collaborat Innovat Ctr, Chengdu, Peoples R China

[4] Sichuan Univ, West China Second Hosp, Dept Pathol, Chengdu, Peoples R China

[5] Sichuan Univ, West China Hosp, Dept Orthoped, Chengdu, Peoples R China

[6] Thomas Jefferson Univ Hosp, Dept Emergency Med, Philadelphia, PA USA

[7] Stanford Univ, Santa Clara Med Ctr, Dept Surg Emergency Med, Santa Clara, CA USA

[8] Sichuan Univ, West China Hosp, Dept Gastrointestinal Surg, Chengdu, Peoples R China

来源：

CANCER RESEARCH | 2017年 / 77卷 / 06期

基金：

中国国家自然科学基金;

关键词：

TUMOR MICROENVIRONMENT; EXPRESSION; CXCL14; GROWTH; TUMORIGENESIS; STROMA; CELLS;

D O I：

10.1158/0008-5472.CAN-16-1615

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

The majority of patients with epithelial ovarian cancer are diagnosed at a late stage when the peritoneal metastases exist; however, there is little knowledge of the metastatic process in this disease setting. In this study, we report the identification of the long noncoding RNA LINC00092 as a nodal driver of metastatic progression mediated by cancer-associated fibroblasts (CAF). Prometastatic properties of CAFs in vitro and in vivo were found to associate with elevated expression of the chemokine CXCL14. In clinical specimens, elevated levels of CXCL14 in CAFs also correlated with poor prognosis. Notably, CXCL14-high CAFs mediated upregulation of LINC00092 in ovarian cancer cells, the levels of which also correlated with poor prognosis in patients. Mechanistic studies showed that LINC00092 bound a glycolytic enzyme, the fructose-2,6biphosphatase PFKFB2, thereby promoting metastasis by altering glycolysis and sustaining the local supportive function of CAFs. Overall, our study uncovered a positive feedback loop in the metabolism of CXCL14-positive CAFs and ovarian cancer cells that is critical for metastatic progression. (C)2017 AACR.

引用

页码：1369 / 1382

页数：14

共 34 条

[1]

[Anonymous], ONCOTARGET

[2] Cancer-Associated Fibroblasts Expressing CXCL14 Rely upon NOS1-Derived Nitric Oxide Signaling for Their Tumor-Supporting Properties [J].

Augsten, Martin ;

Sjoberg, Elin ;

Frings, Oliver ;

Vorrink, Sabine U. ;

Frijhoff, Jeroen ;

Olsson, Eleonor ;

Borg, Ake ;

Ostman, Arne .

CANCER RESEARCH, 2014, 74 (11) :2999-3010

[3] CXCL14 is an autocrine growth factor for fibroblasts and acts as a multi-modal stimulator of prostate tumor growth [J].

Augsten, Martin ;

Hagglof, Christina ;

Olsson, Eleonor ;

Stolz, Claudia ;

Tsagozis, Panagiotis ;

Levchenko, Tetyana ;

Frederick, Mitchell J. ;

Borg, Ake ;

Micke, Patrick ;

Egevad, Lars ;

Ostman, Arne .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2009, 106 (09) :3414-3419

[4] Stromal fibroblasts in cancer initiation and progression [J].

Bhowmick, NA ;

Neilson, EG ;

Moses, HL .

NATURE, 2004, 432 (7015) :332-337

[5] Adipocyte-Derived Fibroblasts Promote Tumor Progression and Contribute to the Desmoplastic Reaction in Breast Cancer [J].

Bochet, Ludivine ;

Lehuede, Camille ;

Dauvillier, Stephanie ;

Wang, Yuan Yuan ;

Dirat, Beatrice ;

Laurent, Victor ;

Dray, Cedric ;

Guiet, Romain ;

Maridonneau-Parini, Isabelle ;

Le Gonidec, Sophie ;

Couderc, Bettina ;

Escourrou, Ghislaine ;

Valet, Philippe ;

Muller, Catherine .

CANCER RESEARCH, 2013, 73 (18) :5657-5668

[6] Rethinking ovarian cancer II: reducing mortality from high-grade serous ovarian cancer [J].

Bowtell, David D. ;

Boehm, Steffen ;

Ahmed, Ahmed A. ;

Aspuria, Paul-Joseph ;

Bast, Robert C., Jr. ;

Beral, Valerie ;

Berek, Jonathan S. ;

Birrer, Michael J. ;

Blagden, Sarah ;

Bookman, Michael A. ;

Brenton, James D. ;

Chiappinelli, Katherine B. ;

Martins, Filipe Correia ;

Coukos, George ;

Drapkin, Ronny ;

Edmondson, Richard ;

Fotopoulou, Christina ;

Gabra, Hani ;

Galon, Jerome ;

Gourley, Charlie ;

Heong, Valerie ;

Huntsman, David G. ;

Iwanicki, Marcin ;

Karlan, Beth Y. ;

Kaye, Allyson ;

Lengyel, Ernst ;

Levine, Douglas A. ;

Lu, Karen H. ;

McNeish, Iain A. ;

Menon, Usha ;

Narod, Steven A. ;

Nelson, Brad H. ;

Nephew, Kenneth P. ;

Pharoah, Paul ;

Powell, Daniel J., Jr. ;

Ramos, Pilar ;

Romero, Iris L. ;

Scott, Clare L. ;

Sood, Anil K. ;

Stronach, Euan A. ;

Balkwill, Frances R. .

NATURE REVIEWS CANCER, 2015, 15 (11) :668-679

[7] Fibroblasts in omentum activated by tumor cells promote ovarian cancer growth, adhesion and invasiveness [J].

Cai, Jing ;

Tang, Huijuan ;

Xu, Linjuan ;

Wang, Xiaoyi ;

Yang, Chun ;

Ruan, Shasha ;

Guo, Jianfeng ;

Hu, Sha ;

Wang, Zehua .

CARCINOGENESIS, 2012, 33 (01) :20-29

[8] Regulation of cancer cell metabolism [J].

Cairns, Rob A. ;

Harris, Isaac S. ;

Mak, Tak W. .

NATURE REVIEWS CANCER, 2011, 11 (02) :85-95

[9] A long noncoding RNA AB073614 promotes tumorigenesis and predicts poor prognosis in ovarian cancer [J].

Cheng, Zhongping ;

Guo, Jing ;

Chen, Li ;

Luo, Ning ;

Yang, Weihong ;

Qu, Xiaoyan .

ONCOTARGET, 2015, 6 (28) :25381-25389

[10] Insights into strategies for optimizing ovarian cancer care [J].

Coleman, Robert L. .

NATURE REVIEWS CLINICAL ONCOLOGY, 2016, 13 (02) :71-72

← 1 2 3 4 →