NDRG1 in Cancer: A Suppressor, Promoter, or Both?

SIMPLE SUMMARY: NDRG1 (N-myc downregulated gene-1) has been reported to suppress metastasis, to be a biomarker of poor outcome, and to be a facilitator of disease progression in a range of different cancers. Characterizing NDRG1 remains challenging due to its pleiotropic functions. This review summarizes the role of NDRG1 in cancer and provides an overview of its expression and function in different cancer types. ABSTRACT: N-myc downregulated gene-1 (NDRG1) has been variably reported as a metastasis suppressor, a biomarker of poor outcome, and a facilitator of disease progression in a range of different cancers. NDRG1 is poorly understood in cancer due to its context-dependent and pleiotropic functions. Within breast cancer, NDRG1 is reported to be either a facilitator of, or an inhibitor of tumour progression and metastasis. The wide array of roles played by NDRG1 are dependent on post-translational modifications and subcellular localization, as well as the cellular context, for example, cancer type. We present an update on NDRG1, and its association with hallmarks of cancer such as hypoxia, its interaction with oncogenic proteins such as p53 as well its role in oncogenic and metastasis pathways in breast and other cancers. We further comment on its functional implications as a metastasis suppressor and promoter, its clinical relevance, and discuss its therapeutic targetability in different cancers.