Abstract 771: CMTM6-mediated maintenance of sarcoma malignancy

Abstract

Abstract Sarcomas are malignant bone and soft tissue tumors that have highly aggressive and metastatic features. To reveal molecular networks associated with sarcomas, comprehensive expression profiles were generated using clinical samples. We identified miR-451a, showing different levels according to the prognosis of Ewing’s sarcoma (EWS) patients. High expression of miR-451a was also associated with good prognoses of patients with other types of sarcomas, suggesting repression of malignant properties across histological subtypes. Although miR-451a did not affect cell proliferation, it strongly repressed migration of EWS cells. Using gene expression analysis, we identified that CMTM6, encoding a chemokine-like membrane protein, was a target of miR-451a. Depletion of CMTM6 suppressed cell migration and induced changes in the expression of genes encoding plasma membrane and secretory proteins. Interestingly, we found high levels of CMTM6 mRNA under low-glucose culture conditions. Unexpectedly, under the same conditions, high extracellular miR-451a levels were observed; this suggested that the glucose level might be a modulator of the miR-451a-CMTM6 axis. Our data suggest that the malignant properties of sarcoma are influenced by the nutrient status of the tumor microenvironment. Citation Format: Yuko Nishiyama, Naoto Tsuchiya. CMTM6-mediated maintenance of sarcoma malignancy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 771.