A Low Membrane Hsp70 Expression in Tumor Cells With Impaired Lactate Metabolism Mediates Radiosensitization by NVP-AUY922.

ABSTRACT: As overexpression and membrane localization of stress proteins together with high lactate levels promote radioresistance in tumor cells, we studied the effect of the Hsp90 inhibitor NVP-AUY922 on the cytosolic and membrane expression of heat shock proteins (HSPs) and radiosensitivity in murine melanoma (B16F10) and human colorectal (LS174T) wildtype (WT) and lactate dehydrogenases A/B double knockout (LDH^-/-) tumor cells. Double knockout for LDHA/B has been found to reduce cytosolic as well as membrane HSP levels, whereas treatment with NVP-AUY922 stimulates the synthesis of Hsp27 and Hsp70, but does not affect membrane Hsp70 expression. Despite NVP-AUY922-inducing elevated levels of cytosolic HSP, radiosensitivity was significantly increased in WT cells and even m

SUBMITTER: Schwab M 

PROVIDER: S-EPMC9022188 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature