Abstract Purpose: Cancer EMT is one of the mechanisms to acquire malignant features including invasiveness, drug resistance and stemness. However, the subsequent mechanism after EMT toward progression has not been fully understood yet. Based on the EMT-centered theory, it is simply thought that the reversal event of EMT, “MET," is caused in the tumor cells at the distant metastatic lesions. However, the molecular mechanism still remains unclear. In this study, we attempted to clarify the “post-EMT” mechanism in tumor cells. Results: Firstly, we prepared tumor cells harvested from metastatic lesions of mice after tumor implantation provisionally as “post-EMT” tumor cells. Murine metastatic melanoma B16-F10 cells were transduced with a neo resistant gene, and were subcutaneously (s.c.) implanted in many C57BL/6 mice to obtain spontaneous tumor metastasis. Three weeks later, various tissues including bone marrow were harvested from the mice, and the single-cell suspensions were cultured in G418-supplemented medium for tumor selection. To characterize the post-EMT tumor cells, RT-PCR, immunostaining and cellular functional assay were conducted. As compared to the primary tumor cells harvested from s.c. tumor tissues, these tumor cells proliferated extremely slowly, and were resistant to chemotherapeutics, but rapidly grew in vivo after implantation. However, these tumor cells were very adhesive accompanied by increase of epithelial markers such as E-cadherin, but not mesenchymal markers such as Snail, indicating epithelial features. In addition, its chemoresistance and in vivo tumorgenesis activity of these tumor cells were superior to those of even Snail-transduced B16-F10 tumor cells, which were harvested from the metastatic lesions in a similar way. DNA microarray analysis revealed the significant upregulation of epithelial markers and drug resistant genes such as c-kit and GDF15 in the post-EMT tumor cells, as compared to those of the Snail transfectant. These imply that “MET” may not be just a reversion of EMT. Conclusions: These results suggest that tumor cells revert into an epithelial state preserving malignant features acquired via EMT even after Snail lost at the metastatic lesions toward progression. We are now attempting to elucidate the molecular mechanism specific for the unique transition utilizing DNA microarray data. Citation Format: Chie Kudo-Saito, Yutaka Kawakami. Cancer MET at the metastatic lesion preserves the malignant features acquired via EMT. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 283. doi:10.1158/1538-7445.AM2013-283