Caffeine affects the biological responses of human hematopoietic cells of myeloid lineage via downregulation of the mTOR pathway and xanthine oxidase activity [PDF]
Correction of human myeloid cell function is crucial for the prevention of inflammatory and allergic reactions as well as leukaemia progression. Caffeine, a naturally occurring food component, is known to display anti-inflammatory effects which have ...
Sumbayev, Vadim V. +22 more
core +2 more sources
Mechanisms and therapeutic opportunities of the ribotoxic stress response in cancer
Cancer cells' high translational demand creates opportunities to therapeutically target ribosome function. Ribosome stalling and collisions activate ZAKα and the ribotoxic stress response (RSR), which can trigger rapid, p53‐independent apoptosis in cancer.
Anastassiya Kim +7 more
wiley +1 more source
Gerosuppression by pan-mTOR inhibitors
Rapamycin slows organismal aging and delays age-related diseases, extending lifespan in numerous species. In cells, rapamycin and other rapalogs such as everolimus suppress geroconversion from quiescence to senescence. Rapamycin inhibits some, but not all, activities of mTOR.
Leontieva, Olga V. +1 more
openaire +2 more sources
Background: Immunosuppressive therapies are important parts of renal transplantation. Objective: To assess the present literature on the effectiveness of early introduction of mTOR inhibitors with or without calcineurin inhibitors (CNI) in renal ...
J Kumar, I Reccia, T Kussano
doaj
Allosteric inhibition enhances the efficacy of ABL kinase inhibitors to target unmutated BCR-ABL and BCR-ABL-T315I [PDF]
Background: Chronic myelogenous leukemia (CML) and Philadelphia chromosome-positive (Ph+) acute lymphatic leukemia (Ph + ALL) are caused by the t(9;22), which fuses BCR to ABL resulting in deregulated ABL-tyrosine kinase activity.
Ruimi, Nili +18 more
core +2 more sources
The VHL tumor suppressor at the crossroad of protein folding, aggregation, and cancer
Mutations, environmental stress, and chaperone dysfunction can destabilize pVHL, promoting its conversion from the native folded state into amyloid‐like assemblies. This transition may contribute to protein storage, cell dormancy, survival, and drug resistance.
Lara Abad +2 more
wiley +1 more source
Dissecting the role of mTOR: Lessons from mTOR inhibitors
Recent years have observed significant advances in our understanding of how the serine/threonine kinase target of rapamycin (TOR) controls key cellular processes such as cell survival, growth and proliferation. Consistent with its role in cell proliferation, the mTOR pathway is frequently hyperactivated in a number of human malignancies and is thus ...
Dowling, Ryan J.O. +3 more
openaire +2 more sources
The role of phospholipase D in modulating the MTOR signaling pathway in polycystic kidney disease.
The mammalian target of rapamycin (mTOR) signaling pathway is aberrantly activated in polycystic kidney disease (PKD). Emerging evidence suggests that phospholipase D (PLD) and its product phosphatidic acid (PA) regulate mTOR activity.
Yang Liu +6 more
doaj +1 more source
Mutant p53R273H disrupts PDPK1 homodimerization and contributes to PDPK1 activation
How mutant p53R273H drives AKT signaling is unclear. We show that p53R273H, but not wild‐type, directly binds PDPK1 via a mutation‐dependent conformational change. This interaction disrupts inhibitory PDPK1 homodimerization and enhances AKT phosphorylation.
Mei Chee Lim +11 more
wiley +1 more source
Targeting the EpCAM‐AXL axis to overcome drug resistance in lung cancer
Lung cancer cells often evade therapy by hijacking signaling pathways. We reveal that cleaved EpCAM (sEpCAM) stabilizes the oncogenic protein AXL, driving NF‐κB and STAT3‐mediated chemoresistance. This EpCAM‐AXL axis identifies a high‐risk patient subset with poor prognosis.
Alexa Guerrero‐Alba +5 more
wiley +1 more source

