Results 91 to 100 of about 1,353,015 (267)

Stimulator of interferon genes agonist augmented antitumor immunity of osimertinib in Egfr‐mutated lung cancer

Molecular Oncology, EarlyView.
Combining osimertinib with the STING agonist ADU‐S100 activates innate and adaptive immunity to overcome the non‐inflamed microenvironment of Egfr‐mutant lung cancer. This combination increases NK and CD8+ T‐cell infiltration, associated with activation of the STING‐IRF3 pathway and local immunogenic cell death.
Jun Nishimura, Tadahiro Kuribayashi, Johannes Brägelmann, Sachi Okawa, Masataka Taoka, Shunta Mori, Tomoka Nishimura, Takaaki Tanaka, Go Makimoto, Kiichiro Ninomiya, Kammei Rai, Eiki Ichihara, Ryohei Katayama, Katsuyuki Hotta, Masahiro Tabata, Yosuke Togashi, Yoshinobu Maeda, Martin L. Sos, Katsuyuki Kiura, Kadoaki Ohashi   +19 more
wiley   +1 more source

Protein Kinase A Regulates Platelet Phosphodiesterase 3A through an A-Kinase Anchoring Protein Dependent Manner

Cells
Platelet activation is critical for haemostasis, but if unregulated can lead to pathological thrombosis. Endogenous platelet inhibitory mechanisms are mediated by prostacyclin (PGI2)-stimulated cAMP signalling, which is regulated by phosphodiesterase 3A (
Jawad S. Khalil, Robert Law, Zaher Raslan, Lih T. Cheah, Matthew S. Hindle, Ahmed A. Aburima, Mark T. Kearney, Khalid M. Naseem   +7 more
doaj   +1 more source

Loss of IGF‐1R impairs DNA‐PKcs recruitment to chromatin leading to defective end‐joining

Molecular Oncology, EarlyView.
IGF‐1R promotes radioresistance by facilitating DNA‐PKcs recruitment to chromatin, enabling non‐homologous end‐joining (NHEJ) repair of double‐strand breaks. Inhibition or loss of IGF‐1R disrupts this recruitment to damage sites, driving compensatory reliance on microhomology‐mediated end‐joining (MMEJ) repair.
Matthew O. Ellis, Jack V. Mills, Wojciech Niedzwiedz, Valentine M. Macaulay   +3 more
wiley   +1 more source

Autophagosomes anchor an AKAP11-dependent regulatory checkpoint that shapes neuronal PKA signaling

The EMBO Journal
Protein Kinase A (PKA) is regulated spatially and temporally via scaffolding of its catalytic (Cα) and regulatory (RI/RII) subunits by the A-kinase-anchoring proteins (AKAP). By binding to an AKAP11 scaffold, PKA engages in poorly understood interactions
Ashley Segura-Roman, Y Rose Citron, Myungsun Shin, Nicole Sindoni, Alex Maya-Romero, Simon Rapp, Claire Goul, Joseph D Mancias, Roberto Zoncu   +8 more
doaj   +1 more source

Finding novel vulnerabilities of hypomorphic BRCA1 alleles

Molecular Oncology, EarlyView.
Synthetic lethality screens performed to identify novel vulnerabilities often model complete gene loss, thereby overlooking patient‐derived hypomorphic mutations. In this study, we have performed genome‐wide CRISPR screens on BRCA1 hypomorphic mutations, showing BRCA1I26A behaves like wild‐type, while BRCA1R1699Q mimics deficiency. Furthermore, we have
Anne Schreuder, Klaas de Lint, Hồ Mỹ Phúc Võ, Mariana M. Góis, Rosalie A. Kampen, Marta San Martin Alonso, Ilse Nootenboom, Veronica Garzero, Tiemen J. Wendel, Rob M. F. Wolthuis, Sylvie M. Noordermeer   +10 more
wiley   +1 more source

Centrosomal actin pool levels regulated by localized PKA set the threshold for T cell polarization

EMBO Reports
T lymphocyte migration triggered by chemokine stimulation is preceded by cell polarization. The acquisition of this asymmetry requires a profound cell rearrangement, particularly of the cytoskeleton.
Morgane Simao, Fabienne Régnier, Clotilde Randriamampita   +2 more
doaj   +1 more source

A versatile kinase mobility shift assay (KiMSA) for PKA analysis and cyclic AMP detection in sperm physiology (and beyond)

Frontiers in Cell and Developmental Biology
The cAMP-dependent protein kinase (PKA) is one of the most extensively distributed kinases among intracellular signal cascades, with a pivotal role in the regulation of various processes, including the capacitation of sperm cells. Traditional assessments
Analia G. Novero, Catalina Curcio, Tomás J. Steeman, Andres Binolfi, Diego Krapf, Mariano G. Buffone, Dario Krapf, Cintia Stival   +7 more
doaj   +1 more source

MITF maintains genome stability in nonmelanocyte lineages

Molecular Oncology, EarlyView.
MITF is essential for melanocyte survival and acts as an oncogene in 10%–20% of melanomas. We show that MITF depletion causes genome instability in nonmelanocytic cells, leading to LATS2‐mediated P53 activation, cell cycle arrest, and apoptosis. This study highlights the role of MITF as a genome maintenance factor beyond the melanocyte lineage. Created
Drifa H. Gudmundsdottir, Adrián López García de Lomana, Thejus B. Venkatesh, Kritika Kirty, Snaevar Sigurdsson, Linda Vidarsdottir, Ramile Dilshat, Erla Sveinbjornsdottir, Snaedis Ragnarsdottir, Daniel H Magnusson, Maria R. Bustos, Eirikur Steingrimsson, Thorkell Gudjonsson, Stefan Sigurdsson   +13 more
wiley   +1 more source

A novel quinazolinone insulin receptor inhibitor and its synergy with an EGFR inhibitor in glucose‐driven glioblastoma

Molecular Oncology, EarlyView.
The novel styrylquinazolinone‐based molecule W1B effectively suppresses glioblastoma by inhibiting IGF1R and EGFR. In high‐glucose microenvironments driving tumor resistance, W1B acts synergistically with the EGFR inhibitor dacomitinib. This combination safely blocks compensatory survival signaling in zebrafish xenograft models. Showcasing promising in
Patryk Rurka, Wioleta Cieślik, Wojciech Płaziński, Katarzyna Stępnik, Anna Boguszewska‐Czubara, Elżbieta Kot, Robert Musioł, Mateusz Jasica, Anna Mrozek‐Wilczkiewicz, Katarzyna Malarz   +9 more
wiley   +1 more source

Liquid biopsy‐based diagnostic evaluation of hypermethylated CpG sites for ovarian cancer diagnosis

Molecular Oncology, EarlyView.
This schematic outlines the workflow from biomarker identification to duplex MethyLight assay validation for epithelial ovarian cancer diagnosis using cfDNA‐based liquid biopsy. Initial screening of hypermethylated CpG candidates (cg02957270, cg10061138 cg00480298, COL2A1) was performed in tissue using ARMS‐PCR, COBRA, qPCR and image analysis. Selected
Deepa Bisht, Sameer Gupta, Amrita Chaurasia, Manisha Sachan   +3 more
wiley   +1 more source