title: Long Noncoding RNA LINC00092 Acts in Cancer-Associated Fibroblasts to Drive Glycolysis and Progression of Ovarian Cancer.
abstract: 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 CAFsin vitroandin vivowere 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-2,6-biphosphatase 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.Cancer Res; 77(6); 1369-82. ©2017 AACR.
authors.affiliation: Department of Obstetrics and Gynecology, Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE and State Key Laboratory of Biotherapy, West China Second Hospital, Sichuan University and Collaborative Innovation Center, Chengdu, P.R. China.
authors.forename: Linjie
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Department of Obstetrics and Gynecology, Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE and State Key Laboratory of Biotherapy, West China Second Hospital, Sichuan University and Collaborative Innovation Center, Chengdu, P.R. China.
authors.forename: Gaili
authors.initials: G
authors.lastname: Ji
authors.affiliation: Department of Obstetrics and Gynecology, Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE and State Key Laboratory of Biotherapy, West China Second Hospital, Sichuan University and Collaborative Innovation Center, Chengdu, P.R. China.
authors.forename: Xiaobing
authors.initials: X
authors.lastname: Le
authors.affiliation: Department of Obstetrics and Gynecology, Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE and State Key Laboratory of Biotherapy, West China Second Hospital, Sichuan University and Collaborative Innovation Center, Chengdu, P.R. China.
authors.forename: Chenlu
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Pathology, West China Second Hospital, Sichuan University, Chengdu, P.R. China.
authors.forename: Lian
authors.initials: L
authors.lastname: Xu
authors.affiliation: Department of Pathology, West China Second Hospital, Sichuan University, Chengdu, P.R. China.
authors.forename: Min
authors.initials: M
authors.lastname: Feng
authors.affiliation: Department of Obstetrics and Gynecology, Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE and State Key Laboratory of Biotherapy, West China Second Hospital, Sichuan University and Collaborative Innovation Center, Chengdu, P.R. China.
authors.forename: Yaguang
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Orthopedics, West China Hospital, Sichuan University, Chengdu, P.R. China.
authors.forename: Huiliang
authors.initials: H
authors.lastname: Yang
authors.affiliation: Department of Obstetrics and Gynecology, Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE and State Key Laboratory of Biotherapy, West China Second Hospital, Sichuan University and Collaborative Innovation Center, Chengdu, P.R. China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Xuan
authors.affiliation: Department of Obstetrics and Gynecology, Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE and State Key Laboratory of Biotherapy, West China Second Hospital, Sichuan University and Collaborative Innovation Center, Chengdu, P.R. China.
authors.forename: Yanfei
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Obstetrics and Gynecology, Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE and State Key Laboratory of Biotherapy, West China Second Hospital, Sichuan University and Collaborative Innovation Center, Chengdu, P.R. China.
authors.forename: Lingzi
authors.initials: L
authors.lastname: Lei
authors.affiliation: Department of Obstetrics and Gynecology, Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE and State Key Laboratory of Biotherapy, West China Second Hospital, Sichuan University and Collaborative Innovation Center, Chengdu, P.R. China.
authors.forename: Qilian
authors.initials: Q
authors.lastname: Yang
authors.affiliation: Department of Emergency Medicine, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania.
authors.forename: Wayne Bond
authors.initials: WB
authors.lastname: Lau
authors.affiliation: Department of Surgery, Emergency Medicine, Kaiser Santa Clara Medical Center, Stanford University, Santa Clara, California.
authors.forename: Bonnie
authors.initials: B
authors.lastname: Lau
authors.affiliation: Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, P.R. China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, P.R. China.
authors.forename: Xiangbing
authors.initials: X
authors.lastname: Deng
authors.affiliation: Department of Obstetrics and Gynecology, Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE and State Key Laboratory of Biotherapy, West China Second Hospital, Sichuan University and Collaborative Innovation Center, Chengdu, P.R. China.
authors.forename: Shaohua
authors.initials: S
authors.lastname: Yao
authors.affiliation: Department of Obstetrics and Gynecology, Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE and State Key Laboratory of Biotherapy, West China Second Hospital, Sichuan University and Collaborative Innovation Center, Chengdu, P.R. China.
authors.forename: Tao
authors.initials: T
authors.lastname: Yi
authors.affiliation: Department of Obstetrics and Gynecology, Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE and State Key Laboratory of Biotherapy, West China Second Hospital, Sichuan University and Collaborative Innovation Center, Chengdu, P.R. China.
authors.forename: Xia
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Department of Obstetrics and Gynecology, Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE and State Key Laboratory of Biotherapy, West China Second Hospital, Sichuan University and Collaborative Innovation Center, Chengdu, P.R. China.
authors.forename: Yuquan
authors.initials: Y
authors.lastname: Wei
authors.affiliation: Department of Obstetrics and Gynecology, Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE and State Key Laboratory of Biotherapy, West China Second Hospital, Sichuan University and Collaborative Innovation Center, Chengdu, P.R. China. taotaovip2005@163.com.
authors.forename: Shengtao
authors.initials: S
authors.lastname: Zhou
mesh_terms: D000818:Animals; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D000072645:Cancer-Associated Fibroblasts / Q000378:metabolism / Q000473:pathology*; D002465:Cell Movement; D049109:Cell Proliferation; D019743:Chemokines, CXC / Q000378:metabolism; D018450:Disease Progression; D005260:Female; D006019:Glycolysis / Q000502:physiology*; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D010534:Peritoneal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000556:secondary*; D025481:Phosphofructokinase-2 / Q000378:metabolism*; D011379:Prognosis; D062085:RNA, Long Noncoding / Q000235:genetics*; D014407:Tumor Cells, Cultured; D059016:Tumor Microenvironment; D023041:Xenograft Model Antitumor Assays
chemical_list: D014408:Biomarkers, Tumor; C118056:CXCL14 protein, human; D019743:Chemokines, CXC; D062085:RNA, Long Noncoding; C555744:PFKFB2 protein, human; D025481:Phosphofructokinase-2