ArticleExperimental & molecular medicine2025
HSF1-DBC1 axis drives prostate cancer progression by activating a metastatic transcriptional program.
Article in Experimental & molecular medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
0 citing papers in PubMed.
No citing paper in PubMed yet.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors.
Funding
Abstract
Heat shock factor 1 (HSF1) is a key stress-protective transcription factor that acts as a guardian of proteostasis. HSF1 also plays multifaceted roles in tumor-associated processes including proliferation and metastasis. HSF1 is frequently overexpressed and activated in a wide range of cancers, including prostate cancer, and hijacked by cancer cells to promote their survival in harsh tumor microenvironments and during metastasis. However, mechanisms underlying the persistent activation of HSF1 and its coregulators in malignancies are largely unknown. Here we show that HSF1 is highly activated and required for metastatic spread and growth of metastatic castration-resistant prostate cancer (mCRPC) cells. The HSF1-driven transcriptional program and its genome occupancy in mCRPC cells were distinct from those of castration-resistant prostate cancer cells and massively reprogrammed during the metastatic progression of castration-resistant prostate cancer cells. In addition, we report DBC1 as a key coregulator of HSF1. DBC1 positively regulated HSF1-mediated transcription and genome-wide chromatin binding of HSF1. Moreover, DBC1 was required for super-enhancer formation and activation of super-enhancer-associated HSF1 target genes, including MMP11, involved in metastasis. Mechanistically, DBC1 activated and stabilized HSF1 by enhancing trimerization and DYRK2-mediated phosphorylation of HSF1 and inhibiting CHIP-mediated HSF1 ubiquitination, thereby increasing the transcriptional activity and genome-wide binding of HSF1. Importantly, DBC1 loss suppresses the metastatic growth of mCRPC cells, and HSF1-DBC1 double-high expression correlated with worse outcomes in patients with mCRPC. Our results highlight the critical role of HSF1 as a metastasis-promoting transcription factor and a novel regulatory mechanism of HSF1 activity and stability by DBC1. Thus, targeting the HSF1-DBC1 axis could be a promising therapeutic strategy for metastatic cancers.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.