The ras-related protein RAB22A interacts with hypoxia-inducible factor 1-alpha (HIF-1α) in MDA-MB-231 breast cancer cells in hypoxia

BackgroundRecent studies suggest that hypoxia-inducible factor 1-alpha (HIF-1 alpha) and the small GTPase protein Ras-related protein Rab-22 A (RAB22A) may be colocalized in the cytoplasm and that as a conequence they may enhance the formation of microvesicles in breast cancer cells under hypoxia. Therefore, we sought to determine whether these two proteins are present in intracellular complexes in breast carcinoma cells.Methods and resultsEvaluation using molecular docking indicated that HIF-1 alpha and RAB22A interact with each other. Co-immunoprecipitation of endogenous or ectopically expressed HIF-1 alpha and RAB22A proteins in MDA-MB-231 breast cancer cells or HEK-293T cells demonstrated that endogenous HIF-1 alpha and RAB22A can form an intracellular complex; however, transiently expressed HIF-1 alpha and RAB22A failed to interact. Investigating RAB22A and HIF-1 alpha interactions in various cancer cell lines under hypoxia may shed light on their roles in cancer cell survival and progression through regulation of intracellular trafficking by HIF-1 alpha under hypoxic conditions.ConclusionsOur study is the first to reveal the potential involvement of HIF-1 alpha in intracellular trafficking through physical interactions with the small GTPase protein RAB22A. We discuss the implications of our work on the role of exosomes and microvesicles in tumor invasiveness.