Abstract 2784: Driver genes network promotes mesenchymal to epithelial transition and organ-specific metastasis

Abstract

Abstract Metastasis, a major characteristic of malignancy, causes high mortality. Accumulating evidence suggests that cancer intends to metastasize to specific organ, however the molecular mechanisms remain unknown. Others and us have demonstrated that epithelial to mesenchymal transition (EMT) plays key roles in initiation of primary tumor adherent, migration, and invasion, whereas mesenchymal to epithelial transition (MET) revokes “sleeping” disseminated tumor cell (DTC) to colonization at distant metastatic organ sites and facilitates the tumor cell proliferation. We have successfully generated the lung-specific metastatic subclones of human prostate cancer PC3 and murine RM1 cells. Through omic bench work and data analysis and comparison with TCGA database, we, for the first time, identified a preliminary network of “driver genes” that potentially promotes the reversible EMT/MET process We utilized cutting-edge tools of data analysis to identify the selected driver genes (LAMA, SPP1, ITGB3, S100A8, SERPINE, DKK2) and further characterized the gene functions via in vitro bioassay of cell proliferation, migration, invasion, cell cycle, and apoptotic testing etc, and in vivo with our unique cell and animal metastatic models. We observed that the rate of organ-specific metastasis was dramatically reduced when these gene expression levels were changed. Finally, we confirmed our findings using TMA slides, Our results may provide novel mechanisms of metastasis and clinical targets of cancer therapy. Supported by NSFC projects 81773146; Guangdong Provincial Key Laboratory of Cell Microenvironment and Disease Research (2017B030301018); JCYJ20170412152943794, JCYJ20170412154619484, JCYJ20170307105128101, JCYJ2017030711041760 Note: This abstract was not presented at the meeting. Citation Format: Ming Chang, Xin Huang, Songjian Lu, Wei Zhang, Weiping Liang, Evan Keller, Xinghua Lu, Jian Zhang. Driver genes network promotes mesenchymal to epithelial transition and organ-specific metastasis [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 2784.