Hsp60/10 related in cancer

Hsp60 has emerged as a critical player in cancer biology, with its expression frequently dysregulated in tumor environments. Elevated levels of Hsp60 have been correlated with poor patient outcomes, including increased metastasis and disease progression. This upregulation is common across many cancer types and has positioned Hsp60 as a potential biomarker for both diagnostic and prognostic purposes. In tumors, Hsp60 appears to support cell survival by helping cancer cells resist apoptotic signals and maintain unchecked proliferation. Rather than fulfilling its traditional role in maintaining mitochondrial protein homeostasis, Hsp60 may instead promote tumor progression by stabilizing oncoproteins and assisting in the folding of misfolded proteins within the mitochondria. The accumulation of these proteins activates the mitochondrial unfolded protein response, which enhances mitochondrial protein quality control by increasing the expression of molecular chaperones, including Hsp60 and its co-chaperone Hsp10. This feedback loop may inadvertently support cancer cell survival. Interestingly, Hsp10 expression is often even higher than Hsp60 in these settings, although it remains less well characterized.

Our lab uses solution-state NMR, single-particle cryo-electron microscopy, and cryo-electron tomography to investigate the protein-folding cycle of Hsp60/10 in health and disease, and to examine cellular responses to known cancer-promoting environmental toxins, such as per- and polyfluoroalkyl substances (PFAS).