Lactate-dependent chaperone-mediated autophagy induces oscillatory HIF-1α activity promoting proliferation of hypoxic cells.

ABSTRACT: Response to hypoxia is a highly regulated process, but little is known about single-cell responses to hypoxic conditions. Using fluorescent reporters of hypoxia response factor-1α (HIF-1α) activity in various cancer cell lines and patient-derived cancer cells, we show that hypoxic responses in individual cancer cells can be highly dynamic and variable. These responses fall into three classes, including oscillatory activity. We identify a molecular mechanism that can account for all three response classes, implicating reactive-oxygen-species-dependent chaperone-mediated autophagy of HIF-1α in a subset of cells. Furthermore, we show that oscillatory response is modulated by the abundance of extracellular lactate in a quorum-sensing-like mechanism. We show that oscillatory HIF-1α activity res

SUBMITTER: Kshitiz 

PROVIDER: S-EPMC10012408 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature