Oncogene Mct-1 Deregulates Oxidative Metabolism And Promotes Tumor Metastasis Via Yy1 Signaling Network

The underlying mechanism of oncogene activation that induces reactive oxygen species (ROS) generation and promotes tumor progression and metastasis is still ambiguous. We now demonstrate that the oncogenic MCT-1 activation protects cells from oxidative damage via increase of YY1 and subsequently enhances EGFR expression and activation. Overexpressing MCT-1 induces cell invasion, intracellular ROS generation and MnSOD expression in mitochondria via YY1 pathway, thus targeting YY1 suppresses cancer cell invasion and blocks EGFR-MnSOD signaling function enhanced by MCT-1. Recapitulating in vitro outcomes, MCT-1 increment promotes tumor angiogenesis, necrosis and metastasis with oxidative metabolism deregulation and malignant microenvironment development in xenograft mice. Clinical data also confirms that MCT-1 enrichment connects to poor survival and prognosis coincident with YY1, EGFR and MnSOD upregulation in patients with lung cancer. Collectively, MCT-1 is a key inducer of YY1-EGFR-MnSOD axis involving the redox mechanism in the process of carcinogenesis. Citation Format: Hong-Yu Tseng, Yen-An Chen, Yi-Rong Chen, Hsin-Ling Hsu. Oncogene MCT-1 deregulates oxidative metabolism and promotes tumor metastasis via YY1 signaling network. [abstract]. In: Proceedings of the AACR Special Conference: Function of Tumor Microenvironment in Cancer Progression; 2016 Jan 7–10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2016;76(15 Suppl):Abstract nr B02.