Hypoxia modulates cellular endocytic pathways and organelles with enhanced cell migration and 3D cell invasion

Abstract

Hypoxia, a decrease in cellular or tissue level oxygen content, is characteristic of most tumours and shown to drive cancer progression by altering multiple subcellular processes. We hypothesized that the cancer cells in a hypoxic environment might have slower proliferation rates and increased invasion and migration rate with altered endocytosis when compared to the cancer cells in the periphery of the tumour mass that experiences normoxic condition. Using chemically induced hypoxia, a short hypoxic exposure increased the uptake of clathrin independent endocytic marker Galectin-3, but a prolonged hypoxic exposure decreased clathrin-independent endocytic uptake, while clathrin mediated endocytosis remained unaffected. Subcellular organelles such as mitochondria showed enhanced intensity to withstand the hypoxic stress, while other organelles such as ER were significantly decreased. The proliferation rates decreased, and the migration and invasion rate increased in cancer cells in hypoxic condition compared to normoxic cancer cells.These data suggest that hypoxia modulates cellular endocytic pathways with decreased proliferation and enhanced cell migration and invasion.