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RAC1P29S Induces a Mesenchymal Phenotypic Switch via Serum Response Factor to Promote Melanoma Development and Therapy Resistance.
(2019-07)
RAC1 P29 is the third most commonly mutated codon in human cutaneous melanoma, after BRAF V600 and NRAS Q61. Here, we study the role of RAC1P29S in melanoma development and reveal that RAC1P29S activates PAK, AKT, and a ...
The Hippo transducer YAP1 transforms activated satellite cells and is a potent effector of embryonal rhabdomyosarcoma formation.
(CELL PRESS, 2014-08-11)
The role of the Hippo pathway effector YAP1 in soft tissue sarcomas is poorly defined. Here we report that YAP1 activity is elevated in human embryonal rhabdomyosarcoma (ERMS). In mice, sustained YAP1 hyperactivity in ...
ALK2 inhibitors display beneficial effects in preclinical models of ACVR1 mutant diffuse intrinsic pontine glioma.
(NATURE PUBLISHING GROUP, 2019-05-09)
Diffuse intrinsic pontine glioma (DIPG) is a lethal childhood brainstem tumour, with a quarter of patients harbouring somatic mutations in ACVR1, encoding the serine/threonine kinase ALK2. Despite being an amenable drug ...
Olaparib and temozolomide in desmoplastic small round cell tumors: a promising combination in vitro and in vivo.
(SPRINGER, 2020-07-01)
PURPOSE: Desmoplastic small round cell tumors (DSRCTs) are highly malignant and very rare soft tissue sarcomas with a high unmet need for new therapeutic options. Therefore, we examined poly(ADP-ribose) polymerase 1 (PARP1) ...
Delayed APC/C activation extends the first mitosis of mouse embryos.
(Springer Science and Business Media LLC, 2017-08-29)
The correct temporal regulation of mitosis underpins genomic stability because it ensures the alignment of chromosomes on the mitotic spindle that is required for their proper segregation to the two daughter cells. Crucially, ...
Expression of the fetal hematopoiesis regulator FEV indicates leukemias of prenatal origin.
(Springer Science and Business Media LLC, 2017-05-01)
The origin of cancers is associated with etiology as well as therapeutics. Several studies reveal that malignancies in children can originate in utero. However, a diagnostic approach to distinguish between cancers initiated ...
Development Refractoriness of MLL-Rearranged Human B Cell Acute Leukemias to Reprogramming into Pluripotency.
(CELL PRESS, 2016-10-11)
Induced pluripotent stem cells (iPSCs) are a powerful tool for disease modeling. They are routinely generated from healthy donors and patients from multiple cell types at different developmental stages. However, reprogramming ...
RPAP3 provides a flexible scaffold for coupling HSP90 to the human R2TP co-chaperone complex.
(Springer Science and Business Media LLC, 2018-04-16)
The R2TP/Prefoldin-like co-chaperone, in concert with HSP90, facilitates assembly and cellular stability of RNA polymerase II, and complexes of PI3-kinase-like kinases such as mTOR. However, the mechanism by which this ...
canSAR: an updated cancer research and drug discovery knowledgebase.
(OXFORD UNIV PRESS, 2016-01-04)
canSAR (http://cansar.icr.ac.uk) is a publicly available, multidisciplinary, cancer-focused knowledgebase developed to support cancer translational research and drug discovery. canSAR integrates genomic, protein, ...
The Mitotic Checkpoint Complex Requires an Evolutionary Conserved Cassette to Bind and Inhibit Active APC/C.
(CELL PRESS, 2016-12-15)
The Spindle Assembly Checkpoint (SAC) ensures genomic stability by preventing sister chromatid separation until all chromosomes are attached to the spindle. It catalyzes the production of the Mitotic Checkpoint Complex ...