PI3K/AKT/mTOR signaling in cancer

Multiple mTOR RNA localization signals regulate subcellular protein synthesis and axonal growth

The paper identifies multiple mTOR RNA localization signals in the 5'UTR and 3'UTR that regulate subcellular mTOR localization, protein synthesis, and axonal growth in mice.

Dual targeting of PDPK1 and BRAF V600E is synthetically lethal

This study shows that targeting PDPK1 and BRAF V600E together is a potent therapy for anaplastic thyroid cancer, leading to tumor regression through synergistic signaling inhibition and apoptosis.

High Resolution Solvated Models Reveal Mechanisms of Allosteric Activation of mTORC1 by RHEB

The paper uses computational methods to generate high-resolution models of mTORC1 with RHEB, revealing structural changes that enable allosteric activation.

PI3K-AKT activation determines oncogenic RAS-induced hypertranscription and replication stress

This study shows that PI3K-AKT activation is required for RAS-induced replication stress and hypertranscription in cancer cells.

Evidence that the protein phosphatase activity of PTEN contributes to embryonic development and tumour suppression in mice

This study shows that PTEN's protein phosphatase activity is essential for embryonic development and tumor suppression in mice, as demonstrated by mutant mice with impaired protein phosphatase activity.

Loss of PIK3CA allows in vitro growth but not in vivo progression of KRAS mutant lung adenocarcinoma in a syngeneic orthotopic implantation model

This study shows that PIK3CA is not required for in vitro growth of KRAS mutant lung cancer cells but is essential for in vivo tumor progression in a syngeneic mouse model.

Suppression of ITPK1 and IPMK activities impairs mTORC1 signaling due to accelerated signal termination and prevents pancreatic β-cell metabolic adaptation to excess glucose

This study shows that reducing ITPK1 and IPMK activities lowers IP5 levels, which shortens mTORC1 signaling and hinders β-cell metabolic adaptation to high glucose.

Targeting PI3Kβ-dependent cancer with a novel small molecule inhibitor, GT220

This paper develops GT220, a selective PI3Kβ inhibitor, showing efficacy in PTEN-deficient cancers while sparing normal cells.

Src promotes tumor cell invasion by hijacking the translation machinery

This study shows Src promotes tumor cell invasion by regulating mRNA translation through eIF3 subunits, essential for invadosome formation and ECM degradation.

Coexistent PTEN and PIK3CA alterations hyperactivate mTORC1 signaling in endometrial cancers and cause their selective sensitivity to mTORC1 inhibition

This study shows that coexisting PTEN and PIK3CA mutations in endometrial cancers hyperactivate mTORC1, making them sensitive to mTORC1 inhibitors but not PI3K or AKT inhibitors.

Structure and function of the yeast amino acid-sensing SEAC-EGOC supercomplex

This study determines the cryo-EM structure of the SEAC-EGOC supercomplex in yeast and shows its role in amino acid signaling to TORC1, revealing how SEACIT and SEACAT regulate this process.

ARP2/3 complex mediates the neuropathology of PTEN-deficient human neural cells downstream of mTORC1 and mTORC2 hyperactivation

This study identifies the ARP2/3 complex as a downstream effector of mTORC1 and mTORC2 hyperactivation in PTEN-deficient neural cells, showing its inhibition can rescue disease phenotypes.

Nuclear Factor Y controls epithelial growth by regulating mTOR in the Drosophila midgut

This study shows that NF-Y regulates mTORC1 activity in Drosophila midgut ISC to control epithelial growth under nutrient-rich conditions.

Functional Characterization of Target of Rapamycin (TOR) Signalling in Physcomitrella

This study investigates TOR signalling in Physcomitrella, showing it positively controls growth, development, chloroplast function, protein synthesis, and cell cycle progression.

Oncogenic PI3Kα variants reveal graded conformational spectrum with mutation-specific cryptic pockets

The paper uses molecular dynamics simulations to show that double mutations in PI3K variants lead to more active conformations and drug-targetable cryptic pockets, suggesting a conformational selection strategy for drug development.

Functional selection in SH3-mediated activation of the PI3 kinase

This study identifies how SH3 domains activate PI3K by engaging in tertiary interactions with p85, revealing a mechanism for controlling activation through functional selection.

ATM-dependent RHEB phosphorylation couples DNA damage to lysosomal mTORC1 signaling to orchestrate the cellular response to genotoxic stress

The paper identifies ATM-dependent RHEB phosphorylation as a mechanism linking DNA damage to lysosomal mTORC1 signaling, which regulates TFEB and lysosome biogenesis during genotoxic stress.

TSC1 phosphorylation by lysosomal mTORC1 establishes a minimal autoregulatory feedback loop

This study identifies TSC1 as a direct mTORC1 substrate, revealing a minimal autoregulatory feedback loop that selectively controls lysosomal mTORC1 signaling.

mTOR signaling governs the formation of epithelial apical projection via S6K1-RhoA and aPKC-Lgl2 axes

This study shows mTOR regulates epithelial apical projections through S6K1-RhoA and aPKC-Lgl2 pathways in zebrafish.

Structural basis for a phosphoinositide-driven mTORC2-AKT positive feedback loop

This study reveals the structural basis of a phosphoinositide-driven mTORC2-AKT positive feedback loop through cryo-EM structures and functional analysis.

Dissociation of the mTOR protein interaction network following neuronal activation is altered by Shank3 mutation

This study shows that Shank3 mutations alter how mTOR signaling networks dissociate in response to neuronal activation, affecting synaptic plasticity.

Regulation of the Rheb GTPase via GATOR1 Complex

This paper identifies a conserved interaction between Rheb and GATOR1 subunits that regulates mTORC1 signaling in response to nutrient stress.

Core passive and facultative mTOR-mediated mechanisms coordinate mammalian protein synthesis and decay

The paper investigates how protein synthesis and decay rates are coordinated in mammalian cells, revealing passive and mTOR-dependent mechanisms that maintain proteome stability.

Rapamycin Differentially Impacts Germline Stem Cell Quiescence Across Diverse Genetic Backgrounds of Drosophila Melanogaster

This study shows that rapamycin affects germline stem cell quiescence differently across genetic backgrounds in Drosophila, with mitophagy playing a key role in quiescence persistence.

mTOR signaling promotes cytokine production in T cells through 3UTR-mediated translation control

This study identifies a novel mTOR-dependent mechanism regulating cytokine production in T cells through 3UTR AU-rich elements and DDX21 binding.

EGFR amplification and PI3K pathway mutations identify a subset of breast cancers that synergistically respond to EGFR and PI3K inhibition

PI3K/mTOR activity sensitizes cancer cells to nucleolar stress

The paper identifies genetic factors that influence cancer cells' sensitivity to nucleolar stress-inducing drugs through CRISPR screens, revealing roles for P53, RB1, and PI3K/mTOR signaling.

A mouse model of PTEN Hamartoma Tumour Syndrome reveals that loss of the nuclear function of PTEN drives macrocephaly, lymphoid overgrowth, and late-onset cancer

This study shows that a specific PTEN mutation causes macrocephaly, lymphoid overgrowth, and late-onset cancer in mice by impairing nuclear PTEN functions, while maintaining normal PI3K/AKT signaling.

Activity and Dynamics of p110α are not Differentially Modulated by Regulatory Subunit Isoforms

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.

Proteomic Analysis of PTEN-Deficient Cells Reveals Src-Mediated Upregulation of EphA2 and Therapeutic Potential of Dual Inhibition

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