PGC1α and VDAC1 expression in endometrial cancer

Wersäll, Ofra Castro; Löfstedt, Lina; Govorov, Igor; Mints, Miriam; Gabrielson, Marike; Shoshan, Maria C.

doi:10.3892/mco.2020.2203

Cited by 8 publications

(6 citation statements)

References 29 publications

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“…The expression PGC1α, a major regulator of mitochondrial biogenesis and function, was signi cantly lower in EC samples than in benign control. Similar result was found in VDAC1, a regulator of apoptosis and metabolite import and export over the mitochondrial outer membrane, suggesting the development of EC involved the altered mitochondrial function [37] . Besides, the level of MRPS18-2 was found to be increased in EC compared with normal endometrium and endometrial hyperplasia, using biopsy-samples of 42 patients.…”

Section: Discussionsupporting

confidence: 73%

“…collected 148 tissue samples of EC and paired benign controls to examine the expression levels of peroxisome proliferator-activated receptor gamma coactivator 1 (PGC1α) and the voltage-dependent anion channel type 1 (VDAC1) [37] . The expression PGC1α, a major regulator of mitochondrial biogenesis and function, was signi cantly lower in EC samples than in benign control.…”

Section: Discussionmentioning

confidence: 99%

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Mitochondrial ribosomal protein L14 (MRPL14) significantly correlated with decreased risk of endometrioid endometrial cancer: A two-sample Mendelian randomization study

Lou,

Wu,

Jiang

et al. 2024

Preprint

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Background The incidence of endometrial cancer (EC)is constantly rising, but its mortality has not been improved in decades. Understanding the molecular mechanism of EC may improve the early diagnosis and develop more targeted therapies. Mitochondrial dysfunction has been currently reported to impact the pathogenesis of various cancers. Thus, this study investigated whether mitochondrial proteins contributed to the development of EC. Methods Using meta-analyses data from genome-wide association studies (GWAS), we conducted a two-sample Mendelian randomization (MR) study on 63 mitochondrial proteins and endometrioid EC (EEC). Inverse-variance weighted (IVW), weighted median, weighted mode, simple mode, and MR-Egger regression approaches were applied. The outcome measure consisted of a GWAS dataset for EEC, comprising a total of 54,884 individuals (8,758 cases and 46,126 controls). Results Of 63 mitochondrial proteins, mitochondrial ribosomal protein L14 (MRPL14) presented a causal association with the decreased susceptibility to EEC by the IVW analysis (MRPL14; odds ratio [OR] = 0.88, 95% confidence interval [CI] = 0.77–0.99, p = 0.039), although neither weighted median method nor MR-Egger regression achieved the same significance. Through Cochran's Q test and visual inspection via funnel plot, the assessment of heterogeneity found no evidence of heterogeneity or asymmetry in our findings, suggesting the absence of directional pleiotropy. Conclusion This MR study found MRPL14 was causally correlated with decreased risk of EEC, implying a novel perspective to understand the mechanism of this malignancy. Further validation is warranted to clarify the effect of MPRL14 in endometrial disorders.

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Section: Discussionsupporting

confidence: 73%

Section: Discussionmentioning

confidence: 99%

Mitochondrial ribosomal protein L14 (MRPL14) significantly correlated with decreased risk of endometrioid endometrial cancer: A two-sample Mendelian randomization study

Lou,

Wu,

Jiang

et al. 2024

Preprint

View full text Add to dashboard Cite

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“…Enhanced mitochondrial biogenesis is typically an adaptive advantage in which proliferating cells meet the increased energy demand [211]; however, one study failed to show increased mitochondrial biogenesis in EC tissue (n = 148) using PGC-1α and VDAC immunostaining when compared to the normal endometrium. This study, however, included both type I and type II ECs [212]. In addition to increased mitochondrial biogenesis, Drp1-mediated mitochondrial fission, BNIP3-mediated mitophagy, and proteolysis were also found to be enhanced in type I EC [6,213].…”

Section: Ec and Mitochondrial Changesmentioning

confidence: 96%

The Role of Genetic Mutations in Mitochondrial-Driven Cancer Growth in Selected Tumors: Breast and Gynecological Malignancies

Czegle

Huang

Soria

et al. 2023

Life

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There is an increasing understanding of the molecular and cytogenetic background of various tumors that helps us better conceptualize the pathogenesis of specific diseases. Additionally, in many cases, these molecular and cytogenetic alterations have diagnostic, prognostic, and/or therapeutic applications that are heavily used in clinical practice. Given that there is always room for improvement in cancer treatments and in cancer patient management, it is important to discover new therapeutic targets for affected individuals. In this review, we discuss mitochondrial changes in breast and gynecological (endometrial and ovarian) cancers. In addition, we review how the frequently altered genes in these diseases (BRCA1/2, HER2, PTEN, PIK3CA, CTNNB1, RAS, CTNNB1, FGFR, TP53, ARID1A, and TERT) affect the mitochondria, highlighting the possible associated individual therapeutic targets. With this approach, drugs targeting mitochondrial glucose or fatty acid metabolism, reactive oxygen species production, mitochondrial biogenesis, mtDNA transcription, mitophagy, or cell death pathways could provide further tailored treatment.

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“…Beyond the role in mitochondrial metabolism, VDAC is also a prognostic biomarker for certain types of human cancer ( Jozwiak et al, 2020 ; Wersall et al, 2021 ). High expression of VDAC1 has been associated with unfavorable outcomes in cancers from lung, head and neck, breast, and liver ( Grills et al, 2011 ; Yang et al, 2019 ; Jozwiak et al, 2020 ).…”

Section: Vdac Opening Mitochondrial Metabolism and Warburg Effectmentioning

confidence: 99%

VDAC Modulation of Cancer Metabolism: Advances and Therapeutic Challenges

2021

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Most anionic metabolites including respiratory substrates, glycolytic adenosine triphosphate (ATP), and small cations that enter mitochondria, and mitochondrial ATP moving to the cytosol, cross the outer mitochondrial membrane (OMM) through voltage dependent anion channels (VDAC). The closed states of VDAC block the passage of anionic metabolites, and increase the flux of small cations, including calcium. Consequently, physiological or pharmacological regulation of VDAC opening, by conditioning the magnitude of both anion and cation fluxes, is a major contributor to mitochondrial metabolism. Tumor cells display a pro-proliferative Warburg phenotype characterized by enhanced aerobic glycolysis in the presence of partial suppression of mitochondrial metabolism. The heterogeneous and flexible metabolic traits of most human tumors render cells able to adapt to the constantly changing energetic and biosynthetic demands by switching between predominantly glycolytic or oxidative phenotypes. Here, we describe the biological consequences of changes in the conformational state of VDAC for cancer metabolism, the mechanisms by which VDAC-openers promote cancer cell death, and the advantages of VDAC opening as a valuable pharmacological target. Particular emphasis is given to the endogenous regulation of VDAC by free tubulin and the effects of VDAC-tubulin antagonists in cancer cells. Because of its function and location, VDAC operates as a switch to turn-off mitochondrial metabolism (closed state) and increase aerobic glycolysis (pro-Warburg), or to turn-on mitochondrial metabolism (open state) and decrease glycolysis (anti-Warburg). A better understanding of the role of VDAC regulation in tumor progression is relevant both for cancer biology and for developing novel cancer chemotherapies.

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PGC1α and VDAC1 expression in endometrial cancer

Cited by 8 publications

References 29 publications

Mitochondrial ribosomal protein L14 (MRPL14) significantly correlated with decreased risk of endometrioid endometrial cancer: A two-sample Mendelian randomization study

Mitochondrial ribosomal protein L14 (MRPL14) significantly correlated with decreased risk of endometrioid endometrial cancer: A two-sample Mendelian randomization study

The Role of Genetic Mutations in Mitochondrial-Driven Cancer Growth in Selected Tumors: Breast and Gynecological Malignancies

VDAC Modulation of Cancer Metabolism: Advances and Therapeutic Challenges

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