Role of HIF-1α/ERRα in Enhancing Cancer Cell Metabolism and Promoting Resistance of Endometrial Cancer Cells to Pyroptosis

Su, Pingping; Yu, Lirui; Mao, Xiaodan; Sun, Pengming

doi:10.3389/fonc.2022.881252

Cited by 11 publications

(11 citation statements)

References 119 publications

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“…In addition, ERRα may be a novel biomarker for predicting the progression of ovarian endometriosis [ 38 ]. Furthermore, as the mechanism of the ERRα-mediated regulation of energy metabolism in EC cells has begun to be revealed, more studies are needed to fully clarify this mechanism [ 39 ].…”

Section: Discussionmentioning

confidence: 99%

ERRα Up-Regulates Invadopodia Formation by Targeting HMGCS1 to Promote Endometrial Cancer Invasion and Metastasis

Tang

et al. 2023

IJMS

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Estrogen-related receptor alpha (ERRα) plays an important role in endometrial cancer (EC) progression. However, the biological roles of ERRα in EC invasion and metastasis are not clear. This study aimed to investigate the role of ERRα and 3-hydroxy-3-methylglutaryl-CoA synthase 1 (HMGCS1) in regulating intracellular cholesterol metabolism to promote EC progression. ERRα and HMGCS1 interactions were detected by co-immunoprecipitation, and the effects of ERRα/HMGCS1 on the metastasis of EC were investigated by wound-healing and transwell chamber invasion assays. Cellular cholesterol content was measured to verify the relationship between ERRα and cellular cholesterol metabolism. Additionally, immunohistochemistry was performed to confirm that ERRα and HMGCS1 were related to EC progression. Furthermore, the mechanism was investigated using loss-of-function and gain-of-function assays or treatment with simvastatin. High expression levels of ERRα and HMGCS1 promoted intracellular cholesterol metabolism for invadopodia formation. Moreover, inhibiting ERRα and HMGCS1 expression significantly weakened the malignant progression of EC in vitro and in vivo. Our functional analysis showed that ERRα promoted EC invasion and metastasis through the HMGCS1-mediated intracellular cholesterol metabolism pathway, which was dependent on the epithelial–mesenchymal transition pathway. Our findings suggest that ERRα and HMGCS1 are potential targets to suppress EC progression.

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Section: Discussionmentioning

confidence: 99%

ERRα Up-Regulates Invadopodia Formation by Targeting HMGCS1 to Promote Endometrial Cancer Invasion and Metastasis

Tang

et al. 2023

IJMS

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“…ERR promotes tumor cell adaptability to hypoxia by increasing glutamine metabolism and lipid de novo synthesis. In conclusion, HIF-1/ERRα interaction can promote tumor cell adaptability to hypoxia, increase cancer cell metabolism, and promote cancer cell resistance to pyrophosphorylation [31]. TFEB promotes EC migration via EMT signaling, regulates wound healing via TFEB-ERR in EK and ECC-1 cells, increases membrane fluidity, and promotes endometrial cancer cell invasion in TFEB-ERR axis-induced lipid reprogramming.…”

Section: Reprogramming Of Lipid Metabolism In Endometrialmentioning

confidence: 91%

Section: Signaling Pathways In the Lipid Metabolism Of Endometrial Ca...mentioning

confidence: 99%

The Regulatory Role of Lipid Metabolism in Endometrial Cancer

Zhang

Han

2022

Journal of Oncology

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Endometrial cancer is the 6th most common carcinoma as well as the 2nd most common malignancy worldwide in women. It is closely related to fat content, and dyslipidemia is among the most significant metabolic changes in this cancer. Therefore, further understanding of the regulation mechanism in lipid metabolism of endometrial cancer is conducive to the development of better therapeutic strategies and methods. Here, we systematically review the signaling pathways that regulate lipid metabolism in endometrial cancer and the research progress of drugs and targeted therapies that act on lipid metabolism by retrieving relevant articles. The underlying mechanism of occurrence and development of endometrial cancer is relatively clear and comprehensively reviewed here. But following more research studies will help to illuminate more specific regulatory roles of lipid metabolism in endometrial cancer and explore new possible mechanisms, prognostic and therapeutic targets, and subsequent drugs. Our review will provide a full view for the following investigation of lipid metabolism in endometrial cancer.

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“…However, it is unknown whether this effect is through direct transcriptional regulation of the receptor expression by HIF. Reports in non-muscle cells suggest an additional layer of regulation through protein-protein interaction between HIF1α and ERRs 62 63 . Both ERRα and ERRγ regulate ERRα expression indicating a mechanism of autoregulation 64 65 .…”

Section: Introductionmentioning

confidence: 99%

Estrogen-related Receptor Signaling in Skeletal Muscle Fitness

Sopariwala¹,

Nguyen²,

Narkar³

2023

Int J Sports Med

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Skeletal muscle is a highly plastic tissue which can alter its metabolic and contractile features, as well as regenerative potential in response to exercise and other conditions. Multiple signaling factors including metabolites, kinases, receptors and transcriptional factors have been studied in the regulation of skeletal muscle plasticity. Recently, estrogen-related receptors (ERRs) have emerged as a critical transcriptional hub in control of skeletal muscle homeostasis. ERRα and ERRγ - the two highly expressed ERR sub-types in the muscle respond to various extracellular cues such as exercise, hypoxia, fasting and dietary factors, in turn regulating gene expression in the skeletal muscle. On the other hand, conditions such as diabetes and muscular dystrophy suppress expression of ERRs in the skeletal muscle, likely contributing to disease progression. We highlight key functions of ERRs in the skeletal muscle including the regulation of fiber type, mitochondrial metabolism, vascularization and regeneration. We also describe how ERRs are regulated in the skeletal muscle, and their interaction with important muscle regulators (e.g. AMPK and PGCs). Finally, we identify critical gaps in our understanding of ERR signaling in the skeletal muscle, and suggest future areas of investigation to advance ERRs as potential targets for function promoting therapeutics in muscle diseases.

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Role of HIF-1α/ERRα in Enhancing Cancer Cell Metabolism and Promoting Resistance of Endometrial Cancer Cells to Pyroptosis

Cited by 11 publications

References 119 publications

ERRα Up-Regulates Invadopodia Formation by Targeting HMGCS1 to Promote Endometrial Cancer Invasion and Metastasis

ERRα Up-Regulates Invadopodia Formation by Targeting HMGCS1 to Promote Endometrial Cancer Invasion and Metastasis

The Regulatory Role of Lipid Metabolism in Endometrial Cancer

Estrogen-related Receptor Signaling in Skeletal Muscle Fitness

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