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Immunological combination treatment holds the key to improving survival in pancreatic cancer.
(2020-11)
Advances in surgery, peri-operative care and systemic chemotherapy have not significantly improved the prognosis of pancreatic cancer for several decades. Early clinical trials of immunotherapy have yielded disappointing ...
Adipocytes disrupt the translational programme of acute lymphoblastic leukaemia to favour tumour survival and persistence.
(NATURE PORTFOLIO, 2021-09-17)
The specific niche adaptations that facilitate primary disease and Acute Lymphoblastic Leukaemia (ALL) survival after induction chemotherapy remain unclear. Here, we show that Bone Marrow (BM) adipocytes dynamically evolve ...
IGF1-mediated human embryonic stem cell self-renewal recapitulates the embryonic niche.
(2020-02-07)
Our understanding of the signalling pathways regulating early human development is limited, despite their fundamental biological importance. Here, we mine transcriptomics datasets to investigate signalling in the human ...
Cancer Burden Is Controlled by Mural Cell-β3-Integrin Regulated Crosstalk with Tumor Cells.
(CELL PRESS, 2020-06-11)
Enhanced blood vessel (BV) formation is thought to drive tumor growth through elevated nutrient delivery. However, this observation has overlooked potential roles for mural cells in directly affecting tumor growth independent ...
Pericyte FAK negatively regulates Gas6/Axl signalling to suppress tumour angiogenesis and tumour growth.
(NATURE PUBLISHING GROUP, 2020-06-04)
The overexpression of the protein tyrosine kinase, Focal adhesion kinase (FAK), in endothelial cells has implicated its requirement in angiogenesis and tumour growth, but how pericyte FAK regulates tumour angiogenesis is ...
Ubiquitylation of MLKL at lysine 219 positively regulates necroptosis-induced tissue injury and pathogen clearance.
(NATURE PORTFOLIO, 2021-06-07)
Necroptosis is a lytic, inflammatory form of cell death that not only contributes to pathogen clearance but can also lead to disease pathogenesis. Necroptosis is triggered by RIPK3-mediated phosphorylation of MLKL, which ...
Mutations in FAM50A suggest that Armfield XLID syndrome is a spliceosomopathy.
(NATURE PORTFOLIO, 2020-07-23)
Intellectual disability (ID) is a heterogeneous clinical entity and includes an excess of males who harbor variants on the X-chromosome (XLID). We report rare FAM50A missense variants in the original Armfield XLID syndrome ...
Serine synthesis pathway inhibition cooperates with dietary serine and glycine limitation for cancer therapy.
(NATURE RESEARCH, 2021-01-14)
Many tumour cells show dependence on exogenous serine and dietary serine and glycine starvation can inhibit the growth of these cancers and extend survival in mice. However, numerous mechanisms promote resistance to this ...
Polθ inhibitors elicit BRCA-gene synthetic lethality and target PARP inhibitor resistance.
(NATURE RESEARCH, 2021-06-17)
To identify approaches to target DNA repair vulnerabilities in cancer, we discovered nanomolar potent, selective, low molecular weight (MW), allosteric inhibitors of the polymerase function of DNA polymerase Polθ, including ...
MCPH1 inhibits Condensin II during interphase by regulating its SMC2-Kleisin interface.
(eLife Sciences Publications, Ltd, 2021-12-01)
Dramatic change in chromosomal DNA morphology between interphase and mitosis is a defining features of the eukaryotic cell cycle. Two types of enzymes, namely cohesin and condensin confer the topology of chromosomal DNA ...