AI Article Synopsis
- Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal cancer with limited treatment options, highlighting the need for new therapeutic strategies.
- Single-cell RNA sequencing of PDAC tumors in KPC mice identified a more aggressive cell cluster with high Hsp90 expression, indicating its role in tumor growth.
- Inhibiting Hsp90 not only stunted tumor growth but also disrupted mitochondrial function, suggesting Hsp90 as a promising target for PDAC therapy.
Article Abstract
Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers, which lacks effective treatment strategies. There is an urgent need for the development of new strategies for PDAC therapy. The genetic and phenotypic heterogeneity of PDAC cancer cell populations poses further challenges in the clinical management of PDAC. In this study, we performed single-cell RNA sequencing to characterize PDAC tumors from KPC mice. Functional studies and clinical analysis showed that PDAC cluster 2 cells with highly Hsp90 expression is much more aggressive than the other clusters. Genetic and pharmacologic inhibition of Hsp90 impaired tumor cell growth both in vitro and in vivo. Further mechanistic study revealed that HSP90 inhibition disrupted the interaction between HSP90 and OPA1, leading to a reduction in mitochondrial cristae amount and mitochondrial energy production. Collectively, our study reveals that HSP90 might be a potential therapeutic target for PDAC.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7930118 | PMC |
| http://dx.doi.org/10.1038/s41389-021-00311-4 | DOI Listing |
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