ESRRA (Estrogen Related Receptor Alpha)

4-hydroxytamoxifen enhances stemness through the NRP/ERRα pathway to enhance breast cancer cell PTX resistance and metastasis.

Combination treatment with XCT790 and endocrine therapies, including the ERα antagonist Tamoxifen or degrader Fulvestrant, produced synergistic antitumor effects. In addition, XCT790 treatment augmented the therapeutic efficacy of chemotherapeutic agents such as Doxorubicin in suppressing ERα-positive breast cancer cell growth both in vitro and in vivo. In summary, our findings reveal that ESRRA is a pivotal regulator of ERSEs and estrogen/ERα-target gene activation, as well as the type I IFN signaling pathway, highlighting its potential as a promising therapeutic target in ERα-positive breast cancer in the clinic.

HGK effectively suppresses ESCC with low toxicity, primarily by inhibiting ESRRA and blocking EMT, highlighting its therapeutic potential.

This study elucidates the possibility that miR-137 subtly modulates metabolic genes in prostate cancer, suggesting its latent therapeutic potential as a biomarker for disease progression.

Curcumin helps maintain the GSH pool and activates glutathione-S-transferase (GST) in rats, thereby potentially facilitating the detoxification and elimination of ATZ. In conclusion, we propose that curcumin's ability to induce CYP3A4, suppress CYP19A1, inhibit EGF signaling, and promote detoxification and elimination of ATZ makes curcumin a promising candidate for a mechanism-based antidote to ATZ toxicity.

Targeting ERRs could represent a promising therapeutic strategy to counteract muscle atrophy in elderly and sedentary subjects. However, further studies are needed to clarify the molecular mechanisms involved and explore the impact of ERRs activation on muscle metabolism.

Based on these findings, the data collated in this study, along with the constructed ensemble models and analytical techniques, provide an effective and reliable framework for the prediction and analysis of ERRα small-molecule ligands. All code for ERRα-Predictor is open source and available at https://github.com/lxiongZ/ERRalpha-Predictor.

The mechanistic link between ESRRG and PD-L1/EMT suggests its potential as a therapeutic target to enhance immunotherapy efficacy. These findings underscore the need for tissue-specific targeting strategies for ERR family members in precision oncology.

Here, we demonstrate a novel role of ERRα in the control of stemness and energetics metabolism in PCSCs via a mechanism of combined transrepression of Zn transporter ZIP1 in reducing intracellular Zn uptake and transactivation of ACO2 (m-aconitase) in completion of TCA cycle. Results also showed that restoration of Zn accumulation by treatment with a Zn ionophore Clioquinol could significantly suppress both in vitro growth of PCSCs and also their in vivo tumorigenicity, implicating that enhanced cellular Zn uptake could be a potential therapeutic approach for targeting PCSCs in advanced prostate cancer.

ERRα emerges as a promising prognostic biomarker in cervical cancer, influencing immune cell infiltration and potentially guiding personalized therapeutic approaches. Future investigations are warranted to delineate the mechanistic pathways through which ERRα contributes to cervical cancer progression and to assess its viability as a target for innovative immunotherapy strategies.

Our study supports that dual nuclear receptor targeting, which simultaneously increases PPARα and diminishes ERRα activity, may represent a viable novel strategy against MASLD.

AIL is a promising downregulator of ERRα, and the mechanism of this downregulation has been elucidated. Additionally, a new regulatory relationship between ERRα and OTUB1 is identified. The research presented in this article is anticipated to yield potential lead compounds for ERRα regulatory agents and to stimulate the development of novel therapeutic strategies designed to modulate ERRα activity for the treatment of TNBC.