ArticleCell death & disease2018
Oncogenic HSP60 regulates mitochondrial oxidative phosphorylation to support Erk1/2 activation during pancreatic cancer cell growth.
Article in Cell death & disease, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers, 1 of them a synthesis that pooled it.
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Who cites it
74 citing papers in PubMed, 1 synthesis or guideline pooled it, 156 citations in OpenAlex.
- Identification of Key Genes Involved in Pancreatic Ductal Adenocarcinoma with Diabetes Mellitus Based on Gene Expression Profiling Analysis.Pathology oncology research : POR · 2021Pooled it
- Review
- Heat Shock Proteins as Targets for Cancer Therapeutics.Journal of clinical medicine · 2026Review
- Melatonin ameliorates inflammation-induced mitochondrial dysfunction and cementoblastic differentiation in cells by regulating the METTL3/LINC01444/HSPD1 axis.Fundamental research · 2026Article
- Imeglimin Exerts Anti-Tumor Activity in Multiple Myeloma Through Affecting Energy Metabolism and Downregulating IL-16 Expression.Cancer medicine · 2026Article
- Heat Shock Proteins in Pancreatic Cancer: Pathogenic Mechanisms and Clinical Implications.Cells · 2025Review
- Mitochondrial unfolded protein response-dependent β-catenin signaling promotes neuroendocrine prostate cancer.Oncogene · 2025Article
- Targeted mitochondrial therapy for pancreatic cancer.Translational oncology · 2025Review
- Chaperonins in Hepatocellular Carcinoma: Unveiling Their Role in Tumor Proliferation and Immune Modulation Through Multiomics Analysis.International journal of genomics · 2025Article
- Comprehensive Analysis of m6A-Related Programmed Cell Death Genes Unveils a Novel Prognostic Model for Lung Adenocarcinoma.Journal of cellular and molecular medicine · 2025Article
- HSP60 controls mitochondrial ATP generation for optimal virus-specific IL-21-producing CD4 and cytotoxic CD8 memory T cell responses.Communications biology · 2024Article
- Article
- A bird's eye view of mitochondrial unfolded protein response in cancer: mechanisms, progression and further applications.Cell death & disease · 2024Review
- Emerging mechanisms and promising approaches in pancreatic cancer metabolism.Cell death & disease · 2024Review
- Systematic analysis of proteome turnover in an organoid model of pancreatic cancer by dSILO.Cell reports methods · 2024Article
- Identification of HSPD1 as a novel invasive biomarker associated with mitophagy in pituitary adenomas.Translational oncology · 2024Article
- Cysteine protease inhibitor 1 promotes metastasis by mediating an oxidative phosphorylation/MEK/ERK axis in esophageal squamous carcinoma cancer.Scientific reports · 2024Article
- Deoxycytidine kinase inactivation enhances gemcitabine resistance and sensitizes mitochondrial metabolism interference in pancreatic cancer.Cell death & disease · 2024Article
- Potential association of HSPD1 with dysregulations in ribosome biogenesis and immune cell infiltration in lung adenocarcinoma: An integrated bioinformatic approach.Cancer biomarkers : section A of Disease markers · 2024Article
- Clinicopathologic significance of heat shock protein 60 as a survival predictor in breast carcinoma.Frontiers in oncology · 2024Article
14 more citing papers are in PubMed but not listed here.
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Authors and funding
14 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
HSP60 is a mitochondrial localized quality control protein responsible for maintaining mitochondrial function. Although HSP60 is considered both a tumor suppressor and promoter in different types of cancer, the role of HSP60 in human pancreatic ductal adenocarcinoma (PDAC) remains unknown. In this study, we demonstrated that HSP60 was aberrantly expressed in human pancreatic cancer tissues and cell lines. Analysis of the Cancer Genome Atlas database revealed that HSP60 expression is positively correlated with pancreatic cancer. Further, knockdown of HSP60 attenuated pancreatic ductal cancer cell proliferation and migration/invasion, whereas ectopic expression of HSP60 increased tumorigenesis. Using an in vivo tumorigenicity assay, we confirmed that HSP60 promoted the growth of pancreatic ductal cancer cells. Functional analyses demonstrated that HSP60 plays a key role in the regulation of mitochondrial function. Mechanistically, both HSP60 knockdown and oxidative phosphorylation (OXPHOS) inhibition by metformin decreased Erk1/2 phosphorylation and induced apoptosis and cell cycle arrest, whereas Erk1/2 reactivation with EGF promoted cell proliferation. Intriguingly, in vitro ATP supplementation partially restored Erk1/2 phosphorylation and promoted proliferation in PDAC cells with HSP60 knockdown and OXPHOS inhibition. These results suggest that mitochondrial ATP is an important sensor of Erk1/2 regulated apoptosis and the cell cycle in PDAC cells. Thus, our findings indicate for the first time that HSP60 may serve as a novel diagnostic target of human pancreatic cancer, and that inhibition of mitochondrial function using drugs such as metformin may be a beneficial therapeutic strategy targeting pancreatic cancer cells with aberrant function of the HSP60/OXPHOS/Erk1/2 phosphorylation axis.
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