Abstract 5536: The metastasis suppressor NME1 regulates stemness in melanoma

Abstract

Abstract Melanoma is a lethal skin cancer that is highly resistant to therapy and prone to metastasize to distant organs. The quiescence melanoma stem cells are believed to account for the resistance to therapies. Traditional chemotherapies designed to target fast-proliferative tumor cells tend to miss quiescent stem cells. The escaped quiescent stem cells may accumulate oncogenic mutation from common mutagenic sources and finally lead to tumor relapse. NME1 is a metastasis suppressor gene that inhibits the metastatic potential in melanoma and other cancers. In this study, we focus on the role of NME1 in the regulation of stemness and quiescence of melanoma stem cells. We find that the genesis and growth of stem cell spheroids derived from melanoma cell lines are abrogated after knockdown of NME1. We also find that the mRNA level of several melanoma stem cell markers are elevated when we knockdown NME1. These results suggest that NME1 regulates the survival and stemness of melanoma stem cells. In addition, we demonstrate that melanoma stem cells are heterogeneous in NME1 expression. Specifically, the NME1 expression is markedly elevated in a highly proliferative subpopulation in the spheroids that express the stem cell markers OCT4, SOX2 and SOX10. Conversely, we observe another subpopulation of these spheroids that exhibits low NME1 expression and is non-proliferative. We hypothesize that this subpopulation consists quiescent melanoma stem cells that are more resistance to therapies, and that their quiescent status is controlled by the level of NME1. We are now employing CRISPR technology to separately study potentials in tumorigenesis, metastasis, and therapy-resistance of the stem cell subpopulations. Citation Format: Ying Wang, David M. Kaetzel. The metastasis suppressor NME1 regulates stemness in melanoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5536. doi:10.1158/1538-7445.AM2017-5536