Abstract 156: Visfatin induces LOX expression and promotes tumor metastasis through the Src/Akt signaling pathway in human chondrosarcoma cells

Abstract

Abstract Chondrosarcoma, a common primary bone malignancy that affects the joints and bones, is associated with metastases in the lung, especially in cases of high-grade chondrosarcoma. The protein lysyl oxidase (LOX) can contribute to tumor growth and metastasis, while the adipokine visfatin is pro-angiogenic and facilitates tumorigenesis as well as metastasis. However, it is unclear as to whether any association exists between visfatin and LOX expression in human chondrosarcoma metastasis. We have discovered that visfatin induces the migration, invasion and increased expression of LOX mRNA and protein in human chondrosarcoma cell lines (JJ012 and SW1353). Pretreatment of these cell lines with Src and Akt inhibitors, or transfecting them with small interfering RNAs (siRNAs), inhibited visfatin-induced chondrosarcoma metastasis and LOX expression. Thus, visfatin promotes chondrosarcoma metastasis by inducing LOX expression via the Src/Akt signaling pathway in the JJ012 cell line. microRNA analysis revealed that visfatin-induced Src/Akt signaling is responsible for downregulating mature miR-26b-5p, which targets the 3' untranslated region (3`UTR) of LOX but does not affect primary and precursor miR-26b-5p expression. This downregulation of miR-26b-5p expression by visfatin was dose-dependent. Pretreatment with Src and Akt inhibitors or transfection with siRNA reversed miR-26b-5p expression. The migration and invasion ability of JJ012 cells was reduced when they were transfected with the miR-26b-5p mimic. In summary, our data demonstrate that visfatin induces LOX expression and promotes chondrosarcoma cell migration and invasion through the Src/Akt signaling pathway, by inhibiting miR-26b-5p. Citation Format: Cheng-Chieh Yu, Chih-Yang Lin, Chih-Hsin Tang. Visfatin induces LOX expression and promotes tumor metastasis through the Src/Akt signaling pathway in human chondrosarcoma cells [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 156.