Antitumor effect of XCT790, an ERRα inverse agonist, on ERα-negative endometrial cancer cells

Kokabu, Tetsuya; Mori, Taisuke; Miyata, Hiroshi; Yoriki, Kaori; Kataoka, Hideki; Tarumi, Yosuke; Kitawaki, Jo

doi:10.1007/s13402-019-00423-5

Cited by 11 publications

(7 citation statements)

References 62 publications

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“…Accordingly, in vivo experiments with H295R xenografts confirmed that pharmacological inhibition of ERRα strongly inhibited ACC cell growth without exerting any marked toxic effect. Our results are supported by additional in vivo studies performed with breast [ 34 ], endometrial [ 35 ] and pancreatic [ 36 ] cancer cells, which altogether point to ERRα as a specific target for the treatment of high energy demanding cells such as tumor cells.…”

Section: Discussionsupporting

confidence: 75%

Estrogen Related Receptor Alpha (ERRα) a Bridge between Metabolism and Adrenocortical Cancer Progression

Avena

Luca

Chimento

et al. 2022

Cancers

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The aim of this study was to investigate the metabolic changes that occur in adrenocortical cancer (ACC) cells in response to the modulation of Estrogen Related Receptor (ERR)α expression and the impact on ACC progression. Proteomics analysis and metabolic profiling highlighted an important role for ERRα in the regulation of ACC metabolism. Stable ERRα overexpression in H295R cells promoted a better mitochondrial fitness and prompted toward a more aggressive phenotype characterized by higher Vimentin expression, enhanced cell migration and spheroids formation. By contrast, a decrease in ERRα protein levels, by molecular (short hairpin RNA) and pharmacological (inverse agonist XCT790) approaches modified the energetic status toward a low energy profile and reduced Vimentin expression and ability to form spheroids. XCT790 produced similar effects on two additional ACC cell lines, SW13 and mitotane-resistant MUC-1 cells. Our findings show that ERRα is able to modulate the metabolic profile of ACC cells, and its inhibition can strongly prevent the growth of mitotane-resistant ACC cells and the progression of ACC cell models to a highly migratory phenotype. Consequently, ERRα can be considered an important target for the design of new therapeutic strategies to fight ACC progression.

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Section: Discussionsupporting

confidence: 75%

Estrogen Related Receptor Alpha (ERRα) a Bridge between Metabolism and Adrenocortical Cancer Progression

Avena

Luca

Chimento

et al. 2022

Cancers

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“…Bonnelye et al collected femoral condyles and tibial plateaus from OA patients after total knee arthroplasty to isolate and culture OA chondrocytes in vitro. OA chondrocytes were treated with the XCT790, a synthetic reverse agonist of ERRα, for 24 h, and the expression index of Sox-9 in OA chondrocytes was dosedependently downregulated by XCT790 (Kokabu et al 2019). This experiment indirectly confirmed that ERRα slows OA chondrocyte loss by participating in cartilage formation.…”

Section: Estrogen-related Receptor αmentioning

confidence: 59%

“…Because long-term use of DES increases the risk of malignant tumors in the reproductive system, this drug was restricted in 1971 (Huo et al 2017;Titus et al 2019;Smith et al 2012). The compound XCT790 has always been regarded as a specific inverse agonist of ERRα, and it has been widely used in experiments related to ERRα (Kokabu et al 2019). It is believed that XCT790 has the ability to disrupt the interaction between ERRα and PGC-1α and inhibit the growth of breast cancer cells.…”

Section: Errs and The Development Of Innovative Drugsmentioning

confidence: 99%

Estrogen-related receptors: novel potential regulators of osteoarthritis pathogenesis

Tang

Liu

Wen

et al. 2021

Mol Med

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Osteoarthritis (OA) is a chronic inflammatory disease that is associated with articular cartilage destruction, subchondral bone alterations, synovitis, and even joint deformity and the loss of joint function. Although current basic research on the pathogenesis of OA has made remarkable progress, our understanding of this disease still needs to be further improved. Recent studies have shown that the estrogen-related receptor (ERR) family members ERRα and ERRγ may play significant roles in the pathogenesis of OA. In this review, we refer to the latest research on ERRs and the pathogenesis of OA, elucidate the structure and physiopathological functions of the ERR orphan nuclear receptor family, and systematically examine the relationship between ERRs and OA at the molecular level. Moreover, we also discuss and predict the capacity of ERRs as potential targets in the clinical treatment of OA.

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“…In 2018, it was proposed that ERRα is a key regulator of cell metabolism and plays an important role in gynecological endocrine-related tumors and energy metabolism ( 101 ). A knockout of ERRα can inhibit the invasion, metastasis, and angiogenesis of EC and promote apoptosis ( 83 , 102 ). Endogenous or exogenous inhibition of the expression and function of ERRα has obvious anticancer effects ( 82 ).…”

Section: Hif-1α and Errα Crosstalk In Cancer Especially In Endometria...mentioning

confidence: 99%

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

Mao

et al. 2022

Front. Oncol.

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Oxygen is critical to energy metabolism, and tumors are often characterized by a hypoxic microenvironment. Owing to the high metabolic energy demand of malignant tumor cells, their survival is promoted by metabolic reprogramming in the hypoxic microenvironment, which can confer tumor cell resistance to pyroptosis. Pyroptosis resistance can inhibit anti-tumor immunity and promote the development of malignant tumors. Hypoxia inducible factor-1α (HIF-1α) is a key regulator of metabolic reprogramming in tumor cells, and estrogen-related receptor α (ERRα) plays a key role in regulating cellular energy metabolism. Therefore, the close interaction between HIF-1α and ERRα influences the metabolic and functional changes in cancer cells. In this review, we summarize the reprogramming of tumor metabolism involving HIF-1α/ERRα. We review our understanding of the role of HIF-1α/ERRα in promoting tumor growth adaptation and pyroptosis resistance, emphasize its key role in energy homeostasis, and explore the regulation of HIF-1α/ERRα in preventing and/or treating endometrial carcinoma patients. This review provides a new perspective for the study of the molecular mechanisms of metabolic changes in tumor progression.

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Antitumor effect of XCT790, an ERRα inverse agonist, on ERα-negative endometrial cancer cells

Cited by 11 publications

References 62 publications

Estrogen Related Receptor Alpha (ERRα) a Bridge between Metabolism and Adrenocortical Cancer Progression

Estrogen Related Receptor Alpha (ERRα) a Bridge between Metabolism and Adrenocortical Cancer Progression

Estrogen-related receptors: novel potential regulators of osteoarthritis pathogenesis

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

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