HSP90 interacts with HMGCR and promotes the progression of hepatocellular carcinoma

Li, Dong; Xue, Liang; Zhang, Cuiying; Li, Hui; Cai, Zhihui; Guo, Ruifang

doi:10.3892/mmr.2018.9667

Cited by 12 publications

(12 citation statements)

References 26 publications

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“…On the other hand, interaction of HMGCR with UbiA prenyltransferase domain-containing protein-1 (UBIAD1) and heat shock protein 90 (HSP90) inhibits HMGCR proteolysis. These PPIs can be referred cancer-related molecular events under conditions of HSP90 and UBIAD1 overexpression which is associated with tumor progression, up-regulation of the mevalonate pathway and cholesterol accumulation [ 165 , 166 ].…”

Section: Discussionmentioning

confidence: 99%

Enzymes in the Cholesterol Synthesis Pathway: Interactomics in the Cancer Context

et al. 2021

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A global protein interactome ensures the maintenance of regulatory, signaling and structural processes in cells, but at the same time, aberrations in the repertoire of protein–protein interactions usually cause a disease onset. Many metabolic enzymes catalyze multistage transformation of cholesterol precursors in the cholesterol biosynthesis pathway. Cancer-associated deregulation of these enzymes through various molecular mechanisms results in pathological cholesterol accumulation (its precursors) which can be disease risk factors. This work is aimed at systematization and bioinformatic analysis of the available interactomics data on seventeen enzymes in the cholesterol pathway, encoded by HMGCR, MVK, PMVK, MVD, FDPS, FDFT1, SQLE, LSS, DHCR24, CYP51A1, TM7SF2, MSMO1, NSDHL, HSD17B7, EBP, SC5D, DHCR7 genes. The spectrum of 165 unique and 21 common protein partners that physically interact with target enzymes was selected from several interatomic resources. Among them there were 47 modifying proteins from different protein kinases/phosphatases and ubiquitin-protein ligases/deubiquitinases families. A literature search, enrichment and gene co-expression analysis showed that about a quarter of the identified protein partners was associated with cancer hallmarks and over-represented in cancer pathways. Our results allow to update the current fundamental view on protein–protein interactions and regulatory aspects of the cholesterol synthesis enzymes and annotate of their sub-interactomes in term of possible involvement in cancers that will contribute to prioritization of protein targets for future drug development.

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Section: Discussionmentioning

confidence: 99%

Enzymes in the Cholesterol Synthesis Pathway: Interactomics in the Cancer Context

et al. 2021

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“…In addition, HSP90 activates HIF-1α and NF-kB, which together enhance the oncogenic events such as cancer cell EMT, invasion, and motility that together confer metastasis of cancer [73]. Furthermore, HSP90 interacts with and inhibits the degradation of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), the rate-limiting enzyme of mevalonate pathway that is essential for cancer progression [74]. Since HSP90 serves to promote the transcription and expression of vascular endothelial growth factor receptors (VEGFRs), the major receptors involved in endothelial cell-dependent tumor angiogenesis, HSP90 overexpression leads to the enhanced proliferation, migration, invasion, and tube cell-dependent tumor angiogenesis in vitro and in vivo [75].…”

Section: Role Of Hsp90 In Cancer Developmentmentioning

confidence: 99%

Heat Shock Proteins: Agents of Cancer Development and Therapeutic Targets in Anti-Cancer Therapy

Yun

Kim

Lim

et al. 2019

Cells

209

158

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Heat shock proteins (HSPs) constitute a large family of molecular chaperones classified by their molecular weights, and they include HSP27, HSP40, HSP60, HSP70, and HSP90. HSPs function in diverse physiological and protective processes to assist in maintaining cellular homeostasis. In particular, HSPs participate in protein folding and maturation processes under diverse stressors such as heat shock, hypoxia, and degradation. Notably, HSPs also play essential roles across cancers as they are implicated in a variety of cancer-related activities such as cell proliferation, metastasis, and anti-cancer drug resistance. In this review, we comprehensively discuss the functions of HSPs in association with cancer initiation, progression, and metastasis and anti-cancer therapy resistance. Moreover, the potential utilization of HSPs to enhance the effects of chemo-, radio-, and immunotherapy is explored. Taken together, HSPs have multiple clinical usages as biomarkers for cancer diagnosis and prognosis as well as the potential therapeutic targets for anti-cancer treatment.

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“…Prenylation of Ras or Rho is critical for their membrane localization and activity (49). Oncogenic roles of HMGCR have been reported in various tumor types, including gastric, liver, and breast cancers (50)(51)(52)(53).…”

Section: Hmg-coa Reductase (Hmgcr)mentioning

confidence: 99%

Aberrant Cholesterol Metabolism in Ovarian Cancer: Identification of Novel Therapeutic Targets

Siu

Ngan

et al. 2021

Front. Oncol.

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Cholesterol is an essential substance in mammalian cells, and cholesterol metabolism plays crucial roles in multiple biological functions. Dysregulated cholesterol metabolism is a metabolic hallmark in several cancers, beyond the Warburg effect. Reprogrammed cholesterol metabolism has been reported to enhance tumorigenesis, metastasis and chemoresistance in multiple cancer types, including ovarian cancer. Ovarian cancer is one of the most aggressive malignancies worldwide. Alterations in metabolic pathways are characteristic features of ovarian cancer; however, the specific role of cholesterol metabolism remains to be established. In this report, we provide an overview of the key proteins involved in cholesterol metabolism in ovarian cancer, including the rate-limiting enzymes in cholesterol biosynthesis, and the proteins involved in cholesterol uptake, storage and trafficking. Also, we review the roles of cholesterol and its derivatives in ovarian cancer and the tumor microenvironment, and discuss promising related therapeutic targets for ovarian cancer.

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HSP90 interacts with HMGCR and promotes the progression of hepatocellular carcinoma

Cited by 12 publications

References 26 publications

Enzymes in the Cholesterol Synthesis Pathway: Interactomics in the Cancer Context

Enzymes in the Cholesterol Synthesis Pathway: Interactomics in the Cancer Context

Heat Shock Proteins: Agents of Cancer Development and Therapeutic Targets in Anti-Cancer Therapy

Aberrant Cholesterol Metabolism in Ovarian Cancer: Identification of Novel Therapeutic Targets

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