Activation of Nm23-H1 to suppress breast cancer metastasis via redox regulation

Abstract

Breast cancer: stopping the spread A small molecule called NMac1 from a plant related to ginger boosts the activity of Nm23-H1, a protein-suppressing metastasis, the spread of cancer cells to other tissues. Metastasis is a primary cause of death in cancer patients. Efforts to develop remedies based on Nm23-H1 treatments have had limited success. Kong-Joo Lee and Bokyung Kim at Ewha Womans University in Seoul, South Korea, reviewed discoveries about the molecular basis of Nm23-H1 action. They report that Nm23-H1 is easily oxidized in cells, preventing it from performing its anti-metastasis function. However, the small molecule NMac1 can stabilize Nm23-H1 by preventing oxidation, and action of NMac1 on Nm23-H1 was shown to prevent breast cancer metastasis in mice. This improved understanding of the molecular mechanism is the first step to potential new anti-metastasis treatments. Non-metastatic protein 23 H1 (Nm23-H1), a housekeeping enzyme, is a nucleoside diphosphate kinase-A (NDPK-A). It was the first identified metastasis suppressor protein. Nm23-H1 prolongs disease-free survival and is associated with a good prognosis in breast cancer patients. However, the molecular mechanisms underlying the role of Nm23-H1 in biological processes are still not well understood. This is a review of recent studies focusing on controlling NDPK activity based on the redox regulation of Nm23-H1, structural, and functional changes associated with the oxidation of cysteine residues, and the relationship between NDPK activity and cancer metastasis. Further understanding of the redox regulation of the NDPK function will likely provide a new perspective for developing new strategies for the activation of NDPK-A in suppressing cancer metastasis.