The HMG (High Mobility Group) Proteins in Cancer Progression

The HMG (high mobility group) proteins are transcription regulators. HMGAs bind to the AT-rich regions of the minor groove of the DNA. HMGA2 is overexpressed in some cancers. It regulates the cell cycle, activates epithelial mesenchymal transition (EMT) and promotes cancer invasion and metastasis. Its expression correlates with clinical stage, nodal involvement and prognosis. HMGA2 operates the PI3K/Akt/mTOR and PI3K/Akt/NF-κB to induce cell proliferation and activate EMT. The Ras/Raf/MEK/ERK is probably involved in EMT activation. So HMGA2 could be prone to the inhibition of these systems. The strategy has included netropsin, which competes with HMGA2 for the AT-rich tracts and prevents its function. Distamycin and berenil also inhibit tumour growth competitively. Unlike HMGA2, HMGA1 targets the AT tracts of NOS2 and inhibits angiogenesis. HMGB1 promotes angiogenesis via NOS2, VEGFs/VEGFRs. It has been targeted by the phytochemical glycyrrhizin. HMGB predominates angiogenic signalling whilst HMGA2 is active in EMT activation, but both would be suitable targets for manipulation of tumour progression.