Long non-coding RNA LINC00092 acts in cancer-associated fibroblasts to drive glycolysis and progression of ovarian cancer
Menée in vitro et in vivo sur des modèles de cancer de l'ovaire, cette étude met en évidence des mécanismes par lesquels, en altérant la glycolyse dans les fibroblastes associés au cancer, un long ARN non codant (LINC00092) favorise le processus métastatique
The majority of patients with epithelial ovarian cancer are diagnosed at a late stage when 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 non-coding RNA LINC00092 as a nodal driver of metastatic progression mediated by cancer-associated fibroblasts (CAF). Pro-metastatic properties of CAF in vitro and in vivo were found to associate with elevated expression of the chemokine CXCL14. In clinical specimens, elevated levels of CXCL14 in CAF also correlated with poor prognosis. Notably, CXCL14-high CAF 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 CAF. Overall, our study uncovered a positive feedback loop in the metabolism of CXCL14-positive CAF and ovarian cancer cells that is critical for metastatic progression.
Cancer Research 2017