DEPDC5 (DEP Domain Containing 5, GATOR1 Subcomplex Subunit)

Moreover, α-hederin bound to the SNX10-DEPDC5 complex and impaired the interaction between SNX10 and DEPDC5, thereby inhibiting CMA-mediated DEPDC5 degradation, impairing the aberrant activation of mTORC1 signaling, and eventually reversing the elevation of glycolysis caused by SNX10 knockdown. Overall, we are the first to demonstrate that SNX10-mediated DEPDC5 degradation is a novel strategy for malignant transformation of normal human IECs, with α-hederin regulated during this process.

Thus, GATOR1 not only participates in the cellular response to amino acid availability but also plays a role in resistance to DNA-damaging anticancer drugs. This novel function of GATOR1 should be taken into account when developing new strategies to combat chemoresistance.

MYC-driven lymphomas lacking GATOR1 display constitutive mTOR pathway activation and are highly sensitive to mTOR inhibitors, both in vitro and in vivo. These findings identify GATOR1 suppression of mTORC1 as a tumor suppressive mechanism in MYC-driven lymphomagenesis and suggest an avenue for therapeutic intervention in GATOR1-deficient lymphomas through mTOR inhibition.

We also hope to stimulate mindful discussions about future possibilities for conscientious and sustainable progress in our evolution toward a genomic model of precision neurosurgery. In the spirit of providing a critical perspective, we hope that we are also adding to the larger opportunity to embed molecular precision into neuroscience care, striving to promote better practice and better outcomes for patients in a global sense.

Validation in a separate cohort of 33 CCA samples confirmed the association of NCOA3 and DEPDC5 with cisplatin response. Our findings suggest that chromosomal aberrations and specific genes may predict cisplatin response in CCA, potentially guiding personalized treatment strategies.

The genetic landscape of infantile epileptic spasms syndrome due to focal malformations comprises germline and somatic variants in a range of genes, with mTORopathies and SLC35A2-related mild malformation of cortical development with oligodendroglial hyperplasia being the major causes. Multimodal data integration incorporating genetic data aids in optimizing diagnostic pathways and can guide surgical decision-making and inform future research and therapeutic interventions.

Sirolimus and everolimus, allosteric mTOR inhibitors, are widely used in transplant medicine and oncology. Despite targeting the underlying disease biology, their efficacy in TSC is not significantly different from other ASM, likely due in part to pharmacokinetic constraints. Next-generation mTOR inhibitors that address these limitations may offer improved response rates, but they are in the preclinical development phase.

This may also provide an advanced prediction of the lesion's phenotype-genotype association in the near future. Thus, digital Neuropathology 3.0 may be the promising next level of laboratory advancement in the realm of neuropathology in focal epilepsy.

More than half of pathogenic somatic variants had a VAF < 5%. Further analysis of the correlation between genetic variants and surgical outcomes will improve patient counseling and may guide postoperative treatment decisions.

This pilot study explores the applicability of LB in GEP-NETs MP evaluation. Further studies with larger cohorts are needed to validate LB and to define the clinical impact.

Mechanistically, Depdc5-deficient CD8+ T cells produced high levels of xanthine oxidase and lipid ROS due to hyper-mTORC1-induced expression of ATF4, leading to spontaneous ferroptosis. Together, our study links DEPDC5-mediated mTORC1 signaling with CD8+ T cell protection from ferroptosis, thereby revealing a novel strategy for enhancing anti-tumor immunity via suppression of ferroptosis.

CMA-mediated DEPDC5 degradation is crucial for lactate/GPR81-induced CRC metastasis, and GA may be a promising candidate for metastasis by inhibiting GPR81 signaling.