NCOA3 (Nuclear Receptor Coactivator 3)

Furthermore, ERRγ functionally competed with major transcriptional coactivators, including steroid receptor coactivators-3 (SRC-3) and p300, thereby attenuating coactivator-enhanced AR-dependent transcription. Collectively, these findings demonstrate that ERRγ functions as a novel corepressor of AR by destabilizing receptor conformation and blocking coactivator recruitment, providing new mechanistic insights into the regulation of AR-mediated transcription.

The framework reframes NRF2 pharmacology around one principle: the most actionable target is often a partner rather than NRF2 itself, with disease context dictating the direction of modulation. We close with five testable hypotheses and a partner-code decision matrix linking disease, biomarker, and candidate target.

This sensitivity to ceramide-induced EnRS and cell death is a vulnerability that could be taken advantage of to treat ET-resistant breast cancer. Implications: This study elucidates the functional relevance of ceramide depletion in endocrine therapy-resistant breast cancer cells.

Accordingly, a phosphorylation-deficient NCOA3 mutant drives CREB/CBP-mediated lipogenesis, whereas genetic or pharmacological NCOA3 inhibition prevents steatosis, hepatic inflammation, and profibrotic signaling. Hence, ULK1-mediated NCOA3 phosphorylation is a fundamental and druggable checkpoint against the entire MASLD spectrum.

Here, we showed that SRC-3KO Tregs exerted a potent antitumor immunity-like effect, capable of eradicating glioblastoma, melanoma, and lung cancer in their respective syngeneic mouse models by generating an anti-tumor immune environment. These results support the translational development of SRC-3-targeted Treg modulation as a safe and effective immunotherapy platform for treatment-refractory cancers.

Hence, a deeper investigation into the molecular mechanisms of SPOP in prostate cancer will provide novel insights into its physiological function in oncogenesis and drug development. In this review, we summarize SPOP's tumor suppressor functions and structural features, upstream regulatory mechanisms, and SPOP-targeting therapeutic strategies in prostate cancer.

This study expands the overlapping morphologic and molecular spectrum of uterine neoplasms resembling uAS showing recurrent fusions (mostly ESR1::NCOA3/2), associated with mostly low-grade histology, lack of heterologous elements and paucity of stromal overgrowth. The nosological relationship of these uAS-like tumors to UTROSCT (driven similarly by ESR1::NCOA3/2 fusions) and to fusion-negative high-grade uAS remains to be verified in future studies utilizing epigenetics and other tools.

Although research on SRC3 in hormone-related cancers is relatively comprehensive, its role in non-hormonal cancers and its clinical translation potential remain insufficiently explored. Future research should examine how SRC3 inhibition affects immune signaling pathways, the tumor and immune microenvironments, tumor heterogeneity, and various aspects of clinical translation, including novel drug development and diagnostic model design.

We showed that this peptide variant binds with a stronger affinity to its target proteins than the wild-type peptide and inhibits CBP/p300 acetylase activity. This peptide variant also modulates interactomes and CBP/p300-mediated gene transcription and exhibits effective antiproliferative activity in cell-based assays.

These genetic alterations were conspicuously absent in primary tumors, suggesting their potential role in metastatic progression. Our findings represent the first demonstration of CNV-driven oncogenic evolution in UTROSCTs, particularly implicating SWI/SNF complex dysregulation in metastatic competence.

Here we present an optimized protocol for ex vivo editing and expansion of mouse Tregs (mTregs). Since a recent study demonstrated the anti-cancer potential of SRC-3 KO mTregs, we use them here as a case study.

Biochanin A exerts a significant inhibitory effect on the biological functions of HepG2 cells.