Nme1, also known as NM23-H1, is a metastasis suppressor gene. It encodes a multifunctional enzyme, nucleoside diphosphate kinase, which is involved in balancing intracellular nucleotide pools, regulating cytoskeletal rearrangement, cell motility, endocytosis, and intracellular trafficking [4]. It has been implicated in various cancer-related pathways, with its down-regulation often associated with increased cancer metastasis.

In breast cancer, HSP90α interacts with Nme1, protecting it from ubiquitin-proteasome-mediated degradation, and overexpression of HSP90α inhibits breast cancer cell metastasis both in vitro and in vivo. A cell-permeable peptide, OPT22, can mimic this function [1]. In melanoma, while Nme1 is classically considered a metastasis suppressor, it was found to promote the expansion of stem-like melanoma cells with enhanced tumor growth and metastatic properties, suggesting a more complex role [3]. In breast cancer, Nme1 down-modulation was identified as a driver of the in-situ-to-invasive transition by regulating MT1-MMP surface clearance [5]. In hepatocellular carcinoma, high Nme1 expression is associated with progression and poor prognosis, and miR-139-5p negatively regulates Nme1 expression to inhibit cell proliferation [2].

In conclusion, Nme1 is a crucial gene in cancer biology, mainly acting as a metastasis suppressor through multiple mechanisms. Its study in various cancer models, especially in relation to its interactions with other molecules and microRNAs, has enhanced our understanding of cancer metastasis and progression, potentially providing new therapeutic targets for metastatic cancers.