PI3K/AKT/mTOR signaling in cancer

This study shows that down-regulating AKT proteins slows mutant-KRAS pancreatic tumor growth more effectively than inhibiting AKT kinase activity.

The paper determines the crystal structure of PTEN-NTE bound to WDR5, revealing a specific binding motif that promotes tumor growth and suggests WDR5 inhibitors as potential cancer therapies.

This study identifies LKB1's role in suppressing growth by activating PIKFYVE to promote EGFR internalization in LUAD.

This study identifies a targetable dependency on noncanonical PI3Kγ signaling in acute leukemias, showing that PI3Kγ inhibition with eganelisib improves survival when combined with cytarabine.

This study uses a TSC2 conditional knockout mouse model to show that mTORC1 activation in thyrocytes inhibits thyroid hormone biosynthesis, promotes growth, and leads to thyroid tumors.

This study shows that p85 loss enhances PI3K/Akt signaling through endosomal p110 activation via MAP4 and PI3P binding.

The paper identifies a nutrient sensor in Drosophila that integrates into the mTORC1 pathway to respond to methionine availability, revealing an evolutionary mechanism for expanding nutrient sensing capabilities.

This study shows that mTORC1 is essential for differentiation of germline stem cells in Drosophila melanogaster testis, with Tor downregulation causing differentiation block and somatic cell activation.

This study investigates the roles of LARP1 and 4EBP1/2 in regulating translation and stability of 5'TOP mRNAs using single-molecule imaging, showing 4EBP1/2's dominant repression and LARP1's selective protection.

The paper engineers yeast TORC1 complexes to reveal distinct functional roles of Tor1- and Tor2-containing TORC1s in growth and lifespan.

This study shows that both mTOR activation and inhibition increase H3K27me3 through distinct mechanisms, and this epigenetic change correlates with the anti-proliferative effects of mTOR inhibitors.

This study shows that targeting both AMPK and mTOR can inhibit prostate cancer metastasis by blocking the metabolic switch required for tumor growth in new environments.

This study shows PTEN's lipid phosphatase activity suppresses melanoma by inhibiting AKT/mTOR signaling and reducing FRA1 expression.

The paper identifies a novel GSK3β/PKCδ/STAT1 pathway that regulates ETV7 transcription and mTORC3 activity in Karpas cells.

This study shows that a phosphorylation-deficient eS6 isoform in Arabidopsis thaliana largely rescues mutant defects in growth, photosynthesis, and gene expression, with minor residual issues.

This paper evaluates the pharmacodynamic effects of AUM001/tinodasertib in preclinical models and human tissues from a Phase 1 study, showing dose-dependent inhibition of eIF4E phosphorylation in tumors and PBMCs.

This study shows GCN5L1 prevents Rictor degradation in cardiac cells under hypoxia by acetylating Rictor, thereby maintaining Akt/mTORC2 signaling and protecting against ischemic injury.

This study shows that both mTORC1 and mTORC2 hyperactivity contribute to epilepsy caused by somatic PTEN loss, and that inhibiting both complexes can normalize brain activity.

This study identifies three distinct pathways by which glucose metabolism activates TORC1 in yeast, including both Rag GTPase-dependent and independent mechanisms.

The paper analyzes the mTOR protein interaction network to reveal its modular organization and how it responds to kinase inhibitors.

This study identifies FOXK2 amplification and overexpression in breast cancer, showing its role in promoting tumor growth, chemoresistance, and synergistic therapeutic responses when targeted with PI3KCA inhibitors.

This paper identifies mTORC2 as the physiological kinase responsible for hydrophobic motif phosphorylation of S6K1, demonstrating its activation after auto-inhibition by mTORC1.

The paper shows that TORC1 inhibits Stm1 to reactivate dormant ribosomes, revealing an evolutionarily conserved mechanism for ribosome preservation.

This study identifies Unkempt as a novel mTORC1 substrate whose phosphorylation regulates cellular morphology by inhibiting its ability to induce bipolar morphology.

The paper shows that TORC1 and PKA activity related to ribosome biogenesis oscillates with the budding yeast cell cycle under constant conditions.

This study investigates how mTORC1 and mTORC2 differentially regulate dopamine neuron morphology and function in mice, revealing distinct effects on structure, excitability, and dopamine output.

The paper identifies FER-mediated tyrosine phosphorylation of IRS4 and its role in activating the PI3K-AKT pathway, contributing to ovarian cancer tumorigenesis.

The paper uses computational models and experiments to show mTORC1 activity depends biphasically on mTORC2 subunit Sin1 and highlights mLST8 as a therapeutic target in breast cancer.

The paper develops a computational model of IGF1R and InsR signaling to reveal context-dependent Akt activity in luminal breast cancer cells and identifies RPS6K as a key regulator.