Abstract

Areas of hypoxia in squamous cell carcinomas of the oral cavity lead to various adaptive mechanisms like anaerobic glycolysis, altered gene expression and deviations in the cellular proteome. These mechanisms not only thwart cellular death but enable rapid progression of growth, culminating in poor prognosis. Amongst a wide number of biomarkers stimulated by hypoxic conditions in oral squamous cell carcinoma (OSCC), the most notable ones are hypoxia-inducible factors (HIF), vascular endothelial growth factors (VEGF) and aquaporins (AQP). In several cancers, including OSCC it has been observed that HIF plays the role of a crucial transcriptional activator. This leads to the downstream expression of several genes that control the process of tumour angiogenesis. The most significant of these genes is VEGF, which has a dominant role as a regulatory gene controlling angiogenesis. VEGFs are a diverse family consisting of which primarily VEGF-A has an essential role in regulating angiogenesis in specific vascular endothelial cells. This is critical for the cellular functions of cancerous tissues to adapt to hypoxic conditions. In addition, VEGF has an immune-regulatory property, thereby modulating immune cell antitumour activity. Another potential biomarker is AQP, a family of transmembrane water channel proteins, that plays a role in transcellular and transepithelial water transport. Unlike AQP1, AQP2, AQP4, AQP5, and AQP8, which exclusively transport water, AQP3, AQP7, AQP9, and AQP10 transport glycerol and other small solutes, and so are termed as “aqua-glyceroporins”. Studies have implicated AQP in the molecular mechanism of oncogenesis across many cancers, where they help in the proliferation of cells, cellular migration, invasiveness and angiogenesis.

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