PI3K/AKT/mTOR signaling in cancer

Distinct sensing of BCAAs by mTOR and c-Myc governs T cell proliferation, independent of catabolism

This study shows that BCAAs are sensed differently by mTOR and c-Myc in T cells, governing proliferation independently of catabolism.

Medulloblastoma-associated mutations in the RNA helicase DDX3X/DED1 cause defects in the translational response to TORC1 inhibition

The paper shows that DDX3X mutations in medulloblastoma disrupt translational responses to TORC1 inhibition, selectively upregulating unstructured mRNAs and promoting tumor growth.

Structure and Function of TM6SF1 Reveal Role in mTORC1 Signaling

This study determines the cryo-EM structure of TM6SF1 and shows it regulates mTORC1 signaling through cholesterol-dependent interaction with LAMTOR1, affecting TFEB activation.

Dietary protein governs the role of insulin signaling in the postprandial regulation of hepatic mTORC1

This study shows dietary protein determines insulin's effect on hepatic mTORC1, and mTORC1 isn't elevated in diet-induced obesity despite metabolic impairments.

Substrate-specific regulation of the mTORC1 pathway by G protein-coupled receptors

This study shows that GPCRs regulate mTORC1 substrates differently, with M5R promoting protein synthesis while allowing lysosome biogenesis.

Insulin receptor substrate 2 (IRS2) confers resistance to PI3K pathway inhibition in PIK3CA mutant breast cancer

This study identifies IRS2 as a mediator of resistance to PI3K pathway inhibitors in PIK3CA mutant breast cancer by sustaining PI3K signaling through FOXO3-mediated regulation.

Simultaneous inhibition of PI3Kα and EZH1/2 suppresses PIK3CA helical domain mutated CRC by promoting IL15-mediated activation of NK cells

This study shows that combining PI3Kα and EZH1/2 inhibitors suppresses PIK3CA-mutated CRC by enhancing IL15-mediated NK cell activation.

Structures of the PI3Kα/KRas complex on lipid bilayers reveal the molecular mechanism of PI3Kα activation

The paper presents cryo-EM structures of the PI3Kα/KRas complex on lipid bilayers, revealing the conformational changes and molecular mechanisms of PI3Kα activation.

NEMF inhibits proliferation and migration of ovarian cancer cells by blocking the PI3K/mTOR pathway

This study shows NEMF inhibits ovarian cancer cell proliferation and migration by blocking the PI3K/mTOR pathway, suggesting it as a potential tumor suppressor.

LARP1 integrates MYC and mTOR signaling to enable anabolic growth during tumor initiation

This study identifies LARP1 as a critical effector linking MYC and mTOR signaling in tumor initiation, showing its role in translating MYC-driven anabolic programs under metabolic permissiveness.

SIRT2 Mediates Integrated Stress Response by Deacetylating and Stabilizing 4EBP1 to Suppress Translation

This study identifies SIRT2 as a regulator of translation by deacetylating and stabilizing 4EBP1, which suppresses protein synthesis under amino acid limitation.

Dual Translational Control in Cardiomyocytes by Heterogeneous mTORC1 and Hypertrophic ERK Activation

This study identifies heterogeneous mTORC1 activity and a novel ERK-dependent pathway driving 4EBP1 phosphorylation in cardiomyocytes during hypertrophy, revealing dual translational control mechanisms.

Structural basis for TORC2 activation

This study determines the cryo-EM structure of yeast TORC2, revealing how phosphoinositides activate it through structural rearrangements involving regulatory subunits.

Nitroxoline-O-protected derivatives inhibit MetAP2 and activate ATF4 through mTORC1 to inhibit cancer cell growth

The paper synthesizes nitroxoline analogs that inhibit MetAP2 and activate ATF4 via mTORC1, showing anti-cancer effects in vitro.

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.

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.

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.

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.

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.

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.

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.

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

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.

Covalent inhibitors of the RAS binding domain of PI3Ka impair tumor growth driven by RAS and HER2

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