Table 2.
Studies on ERRα regulation of glucose and lipid metabolism and promotion of hromone-related tumor progression.
| Author | Cancer type | Main finding |
|---|---|---|
| Fujimoto et al. (74) | EC | ERRα binds to steroid receptor coactivator family without any ligand, drives the transcription activity of target gene, and inhibits estrogen response element-dependent transcription activity in the presence of estrogen, which is related to the growth and progress of EC. |
| McGuirk et al. (75) | BRCA | After using lapatinib to inhibit receptor tyrosine kinase, BRCA cells increased glutamine metabolism and lipid de novo synthesis, while reducing ROS production through the PGC-1α/ERRα axis, promoting cell metabolic adaptation. |
| Deblois et al. (76) | BRCA | ERRα triggers the adaptive change of mitochondrial energy metabolism in drug-resistant cells by increasing glutamine metabolism and detoxification of active oxygen required for cell survival under the condition of therapeutic stress, which leads to lapatinib resistance in BRCA. |
| Zou et al. (77) | PCa | ERRα can cooperate with HIF-1α to regulate angiogenesis and glycolysis, thus promoting the growth of tumor cells under hypoxia |
| Matsushima et al. (78) | EC | SiRNA-ERRα inhibits VEGF and cell proliferation and induces cell cycle arrest during mitosis followed by apoptosis through caspase-3 signal. |
| Park et al. (79) | BRCA | ERRα antagonist destroys mitochondrial function, inhibits lactic acid utilization, damages the activity of cancer cells, and increases the activity of PI3K/mTOR inhibitor. |
| Audet-Walsh et al. (80) | BRCA | PGC-1α/ERRα axis, as an inhibitor of folate cycle metabolism and purine biosynthesis, targets PGC-1α/ERRα to make BRCA cells sensitive to folate treatment. |
| Huang et al. (81) | EC | ERRα directly binds to the promoter of TGFB1, thus increasing its transcription and triggering the migration and invasion of EC cells. |
| Sun et al. (82) | EC | Down-regulation of ERRα can inhibit TFEB, which is mediated by PGC1α and participates in the mTOR signal pathway. In addition, under the mediation of Tcf, down-regulation of ERRα can increase the expression of Oct3/4 and participate in the Wnt signaling pathway. |
| Kokabu et al. (83) | EC | ERRα may play a role in the upstream of Akt and/or regulate the Akt/mTOR signaling pathway in EC. XCT790 significantly inhibits tumor growth and angiogenesis in vivo and induces cell apoptosis. |
| Mao et al. (84) | EC | TAM combined with XCT790 can promote the proliferation inhibition and apoptosis of EC endothelial cells when targeting ERα and ERRα. |
| Yoriki et al. (85) | EC | ERRα inhibits the TGF-β-induced EC metastasis through tumor-stromal interaction. |
| Park et al. (86) | BRCA | ERRα inhibition interferes with pyruvate transport into mitochondria by inhibiting the expression of mitochondrial pyruvate carrier 1, revealing that the NADPH generation pathway is a therapeutic direction for BRCA. |
| Chen et al. (26) | EC | Overexpression of ERRα increases the expression of PGC-1 α and the activity of TFEB in EC cells and promotes EMT. |
| Huang et al. (18) | EC | As a potential agonist of PPARγ, ERRα inhibitor promotes cell proliferation and inhibits apoptosis through the Bcl-2/Caspase3 pathway in EC. |
| Schoepke et al. (87) | PCa | As a selective ERRα/γ inverse agonist, SLU-PP-1072 can inhibit the Warburg effect, change the metabolism and gene expression of PCa cells, and lead to cell cycle disorder and apoptosis. |
| Brindisi et al. (88) | BRCA | Cholesterol and mevalonate are related to the progression, invasiveness, and drug resistance of BRCA by activating the ERRα pathway. |
| Casaburi et al. (89) | BRCA | Cholesterol has been identified as a natural ERRα ligand. High cholesterol content and ERRα activity can promote ERRα-mediated proliferation of BRCA cells and expression of metabolic target genes by producing different cytokines, thus contributing to the inflammatory environment. |
| Li et al. (90) | BRCA | ERRα enhances the resistance of BRCA to lapatinib by targeting the region of SHMT2 promoter and activating transcription and then regulating the metabolic adaptability of mitochondria. |
| Casaburi et al. (91) | BRCA | Cholesterol promotes ERRα-mediated metabolic target gene expression, and increases NADPH level and cell proliferation. |