Heat Shock Proteins and HSF1 in Cancer

Frontiers in Oncology, Journal Year: 2022, Volume and Issue: 12

Published: March 2, 2022

Fitness of cells is dependent on protein homeostasis which maintained by cooperative activities chaperones and proteolytic machinery. Upon encountering protein-damaging conditions, activate the heat-shock response (HSR) involves HSF1-mediated transcriptional upregulation a group - heat shock proteins (HSPs). Cancer experience high levels proteotoxic stress due to production mutated proteins, aneuploidy-induced excess components multiprotein complexes, increased translation rates, dysregulated metabolism. To cope with this chronic state stress, cancers almost invariably upregulate major HSR, including HSF1 individual HSPs. Some oncogenic programs show dependence or coupling particular HSR factor (such as frequent coamplification MYC genes). Elevated HSPs are typically associated drug resistance poor clinical outcomes in various malignancies. The non-oncogene ("addiction") quality controls represents pancancer target treating human malignancies, offering potential enhance efficacy standard targeted chemotherapy immune checkpoint inhibitors. In specific dependencies, can serve alternative targets poorly druggable drivers.

Language: Английский

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Multidimensional pan-cancer analysis of HSPA5 and its validation in the prognostic value of bladder cancer

Heliyon, Journal Year: 2024, Volume and Issue: 10(6), P. e27184 - e27184

Published: Feb. 28, 2024

Endoplasmic reticulum (ER) stress-related genes are closely related to the occurrence, development, and immunotherapy response of tumors. This study provides a comprehensive assessment HSPA5 from pan-cancer perspective using multi-omics data. We analyzed function in multiple tumor types databases. Finally, immunohistochemistry was used examine relationship between expression tissue microarrays 100 patients with bladder cancer prognosis cancer. Using TCGA database, we were able determine that is significantly elevated number common malignancies linked bad prognosis. Cox regression analysis showed high correlated OS, progression free survival (PFS), disease (DFS), special (DSS) adrenocortical carcinoma (ACC). In addition, discovered significant disparities methylation phosphorylation levels various normal tissues. infiltrating cells immune checkpoint genes. highly expressed have poor Our basis for further understanding role ER gene different genesis development. has also been shown be prognostic biomarker patients.

Language: Английский

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A pan-cancer analysis of the prognostic and immunological role of β-actin (ACTB) in human cancers

Bioengineered, Journal Year: 2021, Volume and Issue: 12(1), P. 6166 - 6185

Published: Jan. 1, 2021

Beta-actin (ACTB), a highly conserved cytoskeleton structural protein, has been regarded as common housekeep gene and used reference for years. However, accumulating evidence indicates that ACTB is abnormally expressed in multiple cancers hence changes the to affect invasiveness metastasis of tumors. This study aimed investigate function clinical significance pan-cancer. The role prognosis immune regulation across 33 tumors was explored based on datasets expression omnibus cancer genome atlas. Differential found between adjacent normal tissues, significant associations tumor patients. In most cancers, associated with cells infiltration, checkpoints other modulators. Relevance invasion identified various types by CancerSEA. Moreover, focal adhesion actin regulation-associated pathways were included functional mechanisms ACTB. verified quantitative real-time polymerase chain reaction. Knockdown inhibited head neck squamous carcinoma cell migration NF-κB Wnt/β-catenin pathways. Our first pan-cancer offers insight into prognostic immunological roles different tumors, indicating may be potential biomarker poor infiltration challenged.

Language: Английский

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Targeting HSF1 for cancer treatment: mechanisms and inhibitor development

Theranostics, Journal Year: 2023, Volume and Issue: 13(7), P. 2281 - 2300

Published: Jan. 1, 2023

Heat Shock Factor 1 (HSF1) is a master regulator of heat shock responsive signaling. In addition to playing critical roles in cellular response, emerging evidence suggests that HSF1 also regulates non-heat transcriptional network handle metabolic, chemical, and genetic stress. The function transformation cancer development has been extensively studied recent years. Due important for coping with various stressful states, research on very active. New functions molecular mechanisms underlying these have continuously discovered, providing new targets novel treatment strategies. this article, we review the essential action cells, focusing more recently discovered their reflect advances biology. addition, emphasize regard inhibitors drug development.

Language: Английский

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HSF1 Inhibits Antitumor Immune Activity in Breast Cancer by Suppressing CCL5 to Block CD8+ T-cell Recruitment

Cancer Research, Journal Year: 2023, Volume and Issue: 84(2), P. 276 - 290

Published: Oct. 27, 2023

Abstract Heat shock factor 1 (HSF1) is a stress-responsive transcription that promotes cancer cell malignancy. To provide better understanding of the biological processes regulated by HSF1, here we developed an HSF1 activity signature (HAS) and found it was negatively associated with antitumor immune cells in breast tumors. Knockdown decreased tumor size caused influx several cells, most notably CD8+ T cells. Depletion rescued reduction growth HSF1-deficient tumors, suggesting prevents T-cell to avoid immune-mediated killing. suppressed expression CCL5, chemokine for upregulation CCL5 upon loss significantly contributed recruitment These findings indicate suppresses reducing limit homing tumors prevent destruction, which has implications lack success modulatory therapies cancer. Significance: The reduces infiltration killing, indicating cellular stress responses affect tumor-immune interactions targeting could improve immunotherapies.

Language: Английский

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Insight into the mitochondrial unfolded protein response and cancer: opportunities and challenges

Cell & Bioscience, Journal Year: 2022, Volume and Issue: 12(1)

Published: Feb. 18, 2022

Abstract The mitochondrial unfolded protein response (UPR mt ) is an evolutionarily conserved protective transcriptional that maintains proteostasis by inducing the expression of chaperones and proteases in to various stresses. UPR -mediated program requires participation upstream signaling pathways molecules. factors regulating Caenorhabditis elegans ( C. mammals are both similar different. Cancer cells, as malignant cells with uncontrolled proliferation, exposed challenges from endogenous exogenous Therefore, cancer hijacked exploited for repair mitochondria promotion tumor growth, invasion metastasis. In this review, we systematically introduce inducers , biological processes which participates, mechanisms mammals, cross-tissue signal transduction roles promoting initiation progression. Disrupting targeting constitutes a novel anticancer therapeutic strategy.

Language: Английский

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HSF1 Stimulates Glutamine Transport by Super-Enhancer-Driven lncRNA LINC00857 in Colorectal Cancer

Cancers, Journal Year: 2022, Volume and Issue: 14(16), P. 3855 - 3855

Published: Aug. 9, 2022

Super enhancers are critical for the gene transcription responsible cell fate by interacting with factors. However, relevance of HSF1 to super in tumors remains obscure. We profiled H3K27ac enrichment chromatin immunoprecipitation sequencing. HSF1-mediated lncRNAs were identified lncRNA microarray. The characteristics LINC00857 explored vitro and vivo assays. mechanism was studied via immunoprecipitation, RNA HSF1/ANXA11 knockout mice. found that occupied multiple loci colorectal cancer. screened out an enhancer, lncRNA-LINC00857, which exerts its promoting growth regulating glutamine metabolism. Notably, could stimulate super-enhancer activity acetyltransferase P300 loci, contributing transcription. In turn, nuclear cooperated promote ANXA11 transcription, modulated SLC1A5/ASCT2 protein expression binding competitively miR-122-5p. attenuated cancer formation vivo. Collectively, we shed light on a closely cooperative machinery between enhancers. P300-mediated facilitate expression, SLC1A5-mediated transport. Targeting HSF1/LINC00857/ANXA11 axis may provide valuable therapeutic strategy against

Language: Английский

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Novel mechanism of drug resistance triggered by tumor-associated macrophages through Heat Shock Factor-1 activation

Cancer Immunology Immunotherapy, Journal Year: 2024, Volume and Issue: 73(2)

Published: Jan. 27, 2024

Macrophages constitute a major part of tumor microenvironment, and most existing data demonstrate their ruling role in the development anti-drug resistance cancer cell. One powerful protection system is based on heat shock proteins whose synthesis triggered by activated Heat Shock Factor-1 (HSF1); inhibition HSF1 with CL-43 sensitized A549 lung cells to anti-cancer effect etoposide. Notably, analyzing xenografts mice we observed nest-like pattern co-localization demonstrating enhanced expression macrophages, decided check whether above arrangement has functional value for both cell types. It was found that incubation or DLD1 colon either human monocytes THP1 monocyte-like increased Importantly, same shown when primary cultures tumors were incubated monocytes. To prove implicated caused monocytic cells, generated an subline devoid which did not respond cells. The pharmacological also abolished highlighting new target tumor-associated macrophages proteostasis mechanism.

Language: Английский

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Apolipoprotein E is a Potential Biomarker for Predicting Cancer Prognosis and is Correlated with Immune Infiltration

OncoTargets and Therapy, Journal Year: 2024, Volume and Issue: Volume 17, P. 199 - 214

Published: March 1, 2024

Background: Apolipoprotein E (APOE) is a polymorphic protein that plays role in lipoprotein transformation and metabolism. It involved numerous physiological processes within the body closely associated with tumor growth metastasis. However, of APOE pan-cancer has yet to be evaluated. Therefore, studying association between various cancer types crucial for providing basis individualized treatment strategies clinical prognosis assessment. Methods: We investigated diagnostic prognostic significance across 33 types, as well its correlation mutation burden (TMB) microsatellite instability (MSI). Additionally, we employed ESTIMATE CIBERSORT algorithms analyze potential impact on immune system. Furthermore, gene set enrichment analysis (GSEA) was conducted explore underlying function. Results: Based observations from dataset, expression significantly different normal tissues, simultaneously survival outcomes terms type, annotation, TMB, MSI, TICs abundance. In addition, results also showed may respond variety chemotherapy. Conclusion: The findings this study strongly indicate close development. Moreover, shows promise biomarker predicting response immunotherapy patients pan-cancer. Keywords: apolipoprotein E, APOE, pan-cancer, prognosis, infiltration

Language: Английский

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Multifaceted roles of HSF1 in cell death: A state-of-the-art review

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Journal Year: 2021, Volume and Issue: 1876(2), P. 188591 - 188591

Published: July 14, 2021

Language: Английский

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