Cancer with low cathepsin D levels is susceptible to vacuolar (H⁺ )-ATPase inhibition.

ABSTRACT: Vacuolar (H⁺ )-ATPases (V-ATPases) have important roles in the supply of nutrients to tumors by mediating autophagy and the endocytic uptake of extracellular fluids. Accordingly, V-ATPases are attractive therapeutic targets for cancer. However, the clinical use of V-ATPase inhibitors as anticancer drugs has not been realized, possibly owing to their high toxicity in humans. Inhibition of V-ATPase may be an appropriate strategy in highly susceptible cancers. In this study, we explored markers of V-ATPase inhibitor sensitivity. V-ATPase inhibitors led to pH impairment in acidic intracellular compartments, suppression of macropinocytosis, and decreased intracellular amino acid levels. The sensitivity of cells to V-ATPase inhibitors was correlated with low cathepsin D expression, an

SUBMITTER: Kitazawa S 

PROVIDER: S-EPMC5480082 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature