Glioblastoma cell motility and invasion is regulated by membrane-associated heat shock protein Hsp70.

PURPOSE: Membrane-associated heat shock protein 70 kDa (mHsp70) is specifically localized on the plasma membrane of various malignant tumor cells. In current study, we investigated the role of mHsp70 in motility of glioblastoma cells, which are known to be characterized by a high ability to migrate and invade surrounding brain tissue. METHODS: The presence of mHsp70 on the membrane of patient-derived glioblastoma cells was detected with confocal microscopy, flow cytometry, Western blot, and proteome analysis of lipid rafts. The motility and invasion characteristics were studied using automatic single-cell tracking and transwell analysis with Hsp70 inhibitors. RESULTS: mHsp70 is able to influence the migration and invasion of glioblastoma cells, and the degree of protein expression correlates with motility. The involvement of mHsp70 in the regulation of cell motility is likely to be mediated by interactions with proteins responsible for cytoskeletal remodeling and connection with the extracellular matrix. Moreover, the protein is localized in lipid rafts associating with other members of the HSPs families. The application of small molecule Hsp70 inhibitors PES and JG-98 successfully reduced the migratory and invasive potential, which allowed them to be used as an adjuvant agent in tumor therapy. CONCLUSION: This study expands our understanding of mHsp70 function in cancer cells and contributes to the development of novel approaches to the treatment of malignant tumors. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11060-025-05127-5.