PI3K/AKT/mTOR signaling in cancer

This study investigates how different regulatory subunits modulate p110α activity and finds no significant differences in lipid kinase activity or conformational changes across subunit variants.

This study identifies Src-mediated upregulation of EphA2 in PTEN-deficient cells and shows that combined AKT and Src inhibition synergistically suppresses tumor growth.

This study identifies reduced 4E-BP1 activity and increased cap-dependent protein synthesis as mechanisms of acquired resistance to the AKT inhibitor capivasertib in ovarian cancer.

The paper develops covalent inhibitors targeting the RAS binding domain of PI3Kα, showing efficacy against RAS and HER2-driven tumors without affecting glucose homeostasis.

This paper identifies PI3K pathway activation in Nrf2-driven cisplatin-resistant HNSCC and shows that gedatolisib inhibits tumor growth and re-sensitizes cells to cisplatin.

This study shows HUWE1 enhances mTORC1 activity by promoting Rheb interaction with mTORC1 and supports de novo pyrimidine synthesis via CAD activation.

This study determines the cryo-EM structure of mTORC1 on the lysosomal membrane, showing how growth factor and nutrient signals integrate through three-step recruitment and membrane engagement.

This study identifies CYLD as a deubiquitinase that inhibits mTOR activity by removing K63-linked ubiquitin chains, linking its loss to mTOR hyperactivation and disease.

The paper investigates how different amino acid stresses affect cell survival in murine ES cells, revealing distinct survival strategies and cell death mechanisms.

This study designs, synthesizes, and characterizes a new class of IPMK kinase inhibitors, showing reduced glioblastoma cell growth and a novel InsP5 metabolic signature.

This study reveals the structural mechanism of cholesterol sensing by LYCHOS, showing how cholesterol binding modulates its interaction with GATOR1 to activate mTORC1.

The paper shows that prenatal liver mTORC1 remains active under low glucose, unlike adult liver, due to TRPV4 acetylation preventing FBP-mediated inactivation.

This study uses a live-cell NanoBRET assay to analyze how AKT inhibitors bind to different AKT isoforms and how phosphorylation affects inhibitor binding and cell viability.

This paper elucidates how Gtr1/2 and Pib2 regulate TORC1 in budding yeast through distinct signaling states under different nutrient conditions.

This study identifies the PXXP motif in the ABD of p110β and p110δ as essential for their enhanced oncogenic and signaling activities compared to p110.

The paper identifies 4E-BP and p70 S6K as substrates of PP1-Neurabin/Spinophilin holoenzymes and shows that PDZ domain interactions, not PP1 groove remodeling, determine substrate specificity.

This study shows that PTEN neddylation promotes resistance to CDK4/6 inhibitors in breast cancer by activating the PI3K/Akt pathway and AP-1 transcription factor, and identifies Echinacoside as a potential inhibitor.

This study identifies a reversible basal-like cell state in AKT-inhibitor resistant triple negative breast cancer using multimodal profiling and lineage tracing.

The paper shows that excess methionine triggers growth arrest via Gcn2 activation, which depends on methionine transporter endocytosis.

The paper shows that TYMS protein levels change in a biphasic manner after 5-FU treatment, driven by translation rather than transcription, and identifies SIN1 as a key regulator.

This study identifies CASTOR1 as a tumor suppressor in NSCLC that modulates mTORC1 and KRAS signaling, and shows that its loss promotes tumorigenesis and resistance to KRAS inhibitors.

The paper identifies 13-S-HODE as a tumor suppressive metabolite that inhibits mTOR by binding its ATP-binding domain, thereby suppressing cancer cell growth.

This paper designs and evaluates Dyr726, a brain-penetrant multi-kinase inhibitor that targets PI3Kα, receptor tyrosine kinases, and WNT signaling, showing efficacy in preclinical cancer models.

The paper shows that diet-induced insulin resistance results from increased PTEN expression, which inhibits PI3K signaling, and that PTEN and mTORC1 inhibitors can reverse this effect.

This study identifies SLAP as a tumor suppressor in colorectal cancer that regulates mTORC2 integrity through UBE3C-mediated mLST8 ubiquitination, reducing mTORC2-AKT signaling.

The paper identifies a cryptic pocket in mTOR oncogenic variants through molecular dynamics simulations and suggests designing PI3K-like inhibitors to target this pocket for therapeutic benefit.

The paper shows that RICT-1/Rictor in C. elegans promotes larval germline development via TORC2 signaling and vitellogenins VIT-1 and VIT-3.

This paper develops a yeast-based system to identify TOR inhibitors, demonstrating high sensitivity and effectiveness in detecting known and novel compounds.

This study shows that calmodulin enhances mTORC1 signaling by blocking TSC2-Rheb binding in a Ca2+-dependent manner.

This study maps the proteomic changes in B cells during activation and shows how mTORC1, MYC, and iron regulate protein production and growth.