State of heat shock factor 1 expression as a putative diagnostic marker for oral squamous cell carcinoma

Ishiwata, J; Kasamatsu, Atsushi; Sakuma, Kei; Iyoda, Manabu; Yamatoji, Masanobu; Usukura, Katsuya; Ishige, Shunsaku; Shimizu, Toshihiro; Yamano, Y.; Ogawara, Katsunori; Shiiba, Masashi; Tanzawa, Hideki; Uzawa, Katsuhiro

doi:10.3892/ijo.2011.1178

Cited by 33 publications

(27 citation statements)

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“…High levels of HSF1 and HSPs expression were observed in a broad range of human tumors [ 27 - 30 ]. Moreover, it has been shown that increased HSF1 expression is associated with reduced survival of cancer patients.…”

Section: Discussionmentioning

confidence: 99%

Overexpression of heat shock transcription factor 1 enhances the resistance of melanoma cells to doxorubicin and paclitaxel

et al. 2013

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BackgroundHeat Shock Transcription Factor 1 (HSF1) is activated under stress conditions. In turn, it induces expression of Heat Shock Proteins (HSPs), which are well-known regulators of protein homeostasis. Elevated levels of HSF1 and HSPs were observed in many types of tumors. The aim of the present study was to determine whether HSF1 could have an effect on the survival of cancer cells treated with chemotherapeutic cytotoxic agents.MethodsWe constructed mouse (B16F10) and human (1205Lu, WM793B) melanoma cells overexpressing full or mutant form of human HSF1: a constitutively active one with a deletion in regulatory domain or a dominant negative one with a deletion in the activation domain. The impact of different forms of HSF1 on the expression of HSP and ABC genes was studied by RT-PCR and Western blotting. Cell cultures were treated with increasing amounts of doxorubicin, paclitaxel, cisplatin, vinblastine or bortezomib. Cell viability was determined by MTT, and IC50 was calculated. Cellular accumulation of fluorescent dyes and side population cells were studied using flow cytometry.ResultsCells overexpressing HSF1 and characterized by increased HSPs accumulation were more resistant to doxorubicin or paclitaxel, but not to cisplatin, vinblastine or bortezomib. This resistance correlated with the enhanced efflux of fluorescent dyes and the increased number of side population cells. The expression of constitutively active mutant HSF1, also resulting in HSPs overproduction, did not reduce the sensitivity of melanoma cells to drugs, unlike in the case of dominant negative form expression. Cells overexpressing a full or dominant negative form of HSF1, but not a constitutively active one, had higher transcription levels of ABC genes when compared to control cells.ConclusionsHSF1 overexpression facilitates the survival of melanoma cells treated with doxorubicin or paclitaxel. However, HSF1-mediated chemoresistance is not dependent on HSPs accumulation but on an increased potential for drug efflux by ABC transporters. Direct transcriptional activity of HSF1 is not necessary for increased expression of ABC genes, which is probably mediated by HSF1 regulatory domain.

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Section: Discussionmentioning

confidence: 99%

Overexpression of heat shock transcription factor 1 enhances the resistance of melanoma cells to doxorubicin and paclitaxel

et al. 2013

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“…Elevated nuclear HSF1 expression has also been observed in cervical cancer, colon cancer, lung cancer, pancreatic cancer, prostate cancer, and meningioma [23]. In addition, nuclear HSF1 expression is associated with tumor size in OSCC [95], and with metastasis and poor survival in endometrial cancer [96]. Further characterization of HSF1 activation in cancer was performed using high-throughput ChIP-seq technologies that profiled targeted genes of HSF1 in a broad range of human cancer cell lines and specimens [23].…”

Section: Targeting Fragile Proteostasis In Cancer: Therapeutic Stratementioning

confidence: 99%

HSF1: Guardian of Proteostasis in Cancer

Dai

Sampson

2016

Trends in Cell Biology

174

163

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Proteomic instability is causally related to human diseases. In guarding proteome stability, the heat shock factor 1 (HSF1)-mediated proteotoxic stress response plays a pivotal role. Contrasting with its beneficial role of enhancing cell survival, recent findings have revealed a compelling pro-oncogenic role for HSF1. However, the mechanisms underlying the persistent activation and function of HSF1 within malignancy remain poorly understood. Emerging evidence reveals that oncogenic signaling mobilizes HSF1 and that cancer cells rely on HSF1 to avert proteomic instability and repress tumor-suppressive amyloidogenesis. In aggregate, these new developments suggest that cancer cells endure chronic proteotoxic stress and that proteomic instability is intrinsically associated with malignant state, a characteristic that could be exploited to combat cancer.

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“…Elevated expression of HSF1 has been associated with advanced stages in breast cancer, hepatocellular carcinoma and oral squamous cell carcinoma, suggesting a broad role for the factor these processes [21, 52–54]. It seems likely that the ability of HSF1 to promote cancer cell signaling, to enhance polyploidy and evade cell inactivation pathways likely contribute to tumor progression as well as initiation.…”

Section: Introductionmentioning

confidence: 99%

HSF1, A Versatile Factor in Tumorogenesis

Calderwood¹

2012

CMM

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HSF1 is an essential factor in the acute response to proteotoxic stress, in which it causes rapid transcription of heat shock protein (HSP) genes in order to permit survival of cells and restoration of global protein quality. In addition to this property however, HSF1 is chronically activated or overexpressed in a wide range of cancers and is essential for multiple pathways of malignant transformation. Studies in recent years indicate a remarkable pleiotropy in the properties of HSF1 in cancer. HSF1 functions as a transcription factor for HSP genes, reminiscent of its role in the stress response, and the resultant elevation in HSP levels leads to a reduction in programmed cell death and senescence and permits overexpression of mutated oncogenic protein clients required to fuel tumor growth. In addition HSF1 plays a role as a signal modulator, stimulating kinase activity, regulating energy metabolism and permitting the development of polyploidy in cancer cells. HSF1 can also function as an inhibitor of transcription and in cooperation with NuRD family factors can repress genes that oppose metastasis. Inhibitors of HSF1 are undergoing selection and future studies may see the testing of HSF1 as a target in cancer therapy.

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State of heat shock factor 1 expression as a putative diagnostic marker for oral squamous cell carcinoma

Cited by 33 publications

References 36 publications

Overexpression of heat shock transcription factor 1 enhances the resistance of melanoma cells to doxorubicin and paclitaxel

Overexpression of heat shock transcription factor 1 enhances the resistance of melanoma cells to doxorubicin and paclitaxel

HSF1: Guardian of Proteostasis in Cancer

HSF1, A Versatile Factor in Tumorogenesis

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