HSF1: Guardian of Proteostasis in Cancer

Dai, Chengkai; Sampson, Stephen B.

doi:10.1016/j.tcb.2015.10.011

Cited by 180 publications

(177 citation statements)

References 104 publications

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“…In addition, in vitro studies have shown that HSF1 has multiple carcinogenic effects, such as regulating cell proliferation, migration and invasion, and inducing EMT. These results were supported by a recent study which showed that HSF1 is important for tumor progression and that it enhances cell migration and plays a critical role in EMT . These data may provide an explanation for the high expression of HSF1 in CAFs in promoting OSCC progression.…”

Section: Discussionsupporting

confidence: 79%

Heat shock factor 1 in cancer‐associated fibroblasts is a potential prognostic factor and drives progression of oral squamous cell carcinoma

et al. 2019

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Heat shock factor 1 ( HSF 1) is highly expressed in various malignancies and is a potential modulator of tumor progression. Emerging evidence suggests that HSF 1 activation in stromal cells is closely related to poor patient prognosis. However, the role of HSF 1 in oral squamous cell carcinoma ( OSCC ) remains elusive. We aimed to investigate the function of HSF 1 in cancer‐associated fibroblasts ( CAFs ) of the tumor microenvironment ( TME ) and in tumor development. In the present study, we found that HSF 1 was highly expressed in both CAFs and tumor cells, and was significantly correlated with poor prognosis and overall survival. Moreover, HSF 1 overexpression in CAFs resulted in a fibroblast‐like phenotype of Cal27 cells, induced epithelial‐mesenchymal transition ( EMT ), and promoted proliferation, migration and invasion in Cal27 cells. HSF 1 knockdown attenuated features of CAFs and reduced EMT , proliferation, migration and invasion in Cal27 cells. Furthermore, HSF 1 in CAFs promoted tumor growth in nude mice. Taken together, these data suggest that HSF 1 expression in CAFs drive OSCC progression, and could serve as an independent prognostic marker of patients with OSCC . Thus, HSF 1 is a potent mediator of OSCC malignancy.

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Section: Discussionsupporting

confidence: 79%

Heat shock factor 1 in cancer‐associated fibroblasts is a potential prognostic factor and drives progression of oral squamous cell carcinoma

et al. 2019

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“…However, this lethality can be rescued by additional gain of chromosome 13, carrying α-tubulin genes, thus restoring the stoichiometry of α/β-tubulin dimers (Anders et al, 2009). Another consequence of unbalanced gene expression could be a general loss of proteostasis (Dai and Sampson; Kaushik and Cuervo, 2015). It is thought that aneuploid cells, carrying extra copies of one or several chromosomes, would exhibit an overproduction of proteins relative to the chaperone systems needed to fold nascent polypeptides or the degradation systems that remove misfolded or damaged proteins (Donnelly and Storchová, 2015).…”

Section: Aneuploidy-associated Stressmentioning

confidence: 99%

Cellular Stress Associated with Aneuploidy

et al. 2018

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Aneuploidy, chromosome stoichiometry that deviates from exact multiples of the haploid compliment of an organism, exists in eukaryotic microbes, several normal human tissues, and the majority of solid tumors. Here, we review the current understanding about the cellular stress states that may result from aneuploidy. The topics of aneuploidy-induced proteotoxic, metabolic, replication, and mitotic stress are assessed in the context of the gene dosage imbalance observed in aneuploid cells. We also highlight emerging findings related to the downstream effects of aneuploidy-induced cellular stress on the immune surveillance against aneuploid cells.

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“…These pathways have been shown to be dynamically regulated throughout melanoma progression to increase intrinsic adaptations against proteotoxic stress, to accommodate the high metabolic demands of these cancer cells, and to modulate the interface with stromal cells within the tumor microenvironment. However, unlike other well-documented types of stress involved in malignant behavior, such as genotoxic, oxidative, and metabolic stress in cancer cells, much less is known about the mechanisms regulating proteostatic stress and how perturbations in the proteome of cancer cells, and more specifically in melanoma, affect disease progression, despite its prominent manifestation in other human disorders (29). …”

Section: Melanomamentioning

confidence: 99%

Adapt, Recycle, and Move on: Proteostasis and Trafficking Mechanisms in Melanoma

et al. 2016

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Melanoma has emerged as a paradigm of a highly aggressive and plastic cancer, capable to co-opt the tumor stroma in order to adapt to the hostile microenvironment, suppress immunosurveillance mechanisms, and disseminate. In particular, oncogene- and aneuploidy-driven dysregulations of proteostasis in melanoma cells impose a rewiring of central proteostatic processes, such as the heat shock and unfolded protein responses, autophagy, and the endo-lysosomal system, to avoid proteotoxicity. Research over the past decade has indicated that alterations in key nodes of these proteostasis pathways act in conjunction with crucial oncogenic drivers to increase intrinsic adaptations of melanoma cells against proteotoxic stress, modulate the high metabolic demand of these cancer cells and the interface with other stromal cells, through the heightened release of soluble factors or exosomes. Here, we overview and discuss how key proteostasis pathways and vesicular trafficking mechanisms are turned into vital conduits of melanoma progression, by supporting cancer cell’s adaptation to the microenvironment, limiting or modulating the ability to respond to therapy and fueling melanoma dissemination.

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HSF1: Guardian of Proteostasis in Cancer

Cited by 180 publications

References 104 publications

Heat shock factor 1 in cancer‐associated fibroblasts is a potential prognostic factor and drives progression of oral squamous cell carcinoma

Heat shock factor 1 in cancer‐associated fibroblasts is a potential prognostic factor and drives progression of oral squamous cell carcinoma

Cellular Stress Associated with Aneuploidy

Adapt, Recycle, and Move on: Proteostasis and Trafficking Mechanisms in Melanoma

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