Results 121 to 130 of about 319,384 (262)

Finding novel vulnerabilities of hypomorphic BRCA1 alleles

open access: yesMolecular 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   +10 more
wiley   +1 more source

MITF maintains genome stability in nonmelanocyte lineages

open access: yesMolecular 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   +13 more
wiley   +1 more source

Oncogenic DMTF1β promotes cancer cell motility by regulating autophagy through ULK1 stabilization

open access: yesMolecular Oncology, EarlyView.
In the current study, we demonstrate that the oncogene DMTF1β regulates ULK1 stability by reducing its proteasomal degradation in cancer cells. This stabilization enables ULK1 to induce autophagy, which in turn facilitates cancer cell migration. Consequently, reduced DMTF1β levels lead to decreased autophagy and impaired cancer cell migration.
Jun Xu   +13 more
wiley   +1 more source

Loss of proton‐sensing TDAG8 increases tumor progression in mouse models of colon cancer

open access: yesMolecular Oncology, EarlyView.
Loss of the pH‐sensing receptor TDAG8 accelerates colorectal cancer progression in mice. Animals lacking TDAG8 expression had increased tumor growth, DNA damage, and recruitment of tumor‐associated immune cells, including macrophages, neutrophils, and monocytes.
Ermanno Malagola   +11 more
wiley   +1 more source

Epigenetic heterogeneity and plasticity in therapy‐induced tumor states through single‐cell multi‐omics

open access: yesMolecular Oncology, EarlyView.
Single‐cell multi‐omics reveals epigenetic heterogeneity across therapy‐adaptive tumor states, including quiescent/dormant, drug‐tolerant persister, and EMT‐like phenotypes. By linking regulatory features with state‐associated biomarkers, these approaches inform biomarker‐guided therapeutic strategies for evolving tumors.
Hee Jung Kim   +3 more
wiley   +1 more source

Spatial and single‐nuclei transcriptomics reveals idiosyncratic and generic patterns in papillary and anaplastic thyroid cancers

open access: yesMolecular Oncology, EarlyView.
Matched spatial transcriptomics and single‐nuclei RNA‐seq were generated for anaplastic and BRAFV600E papillary thyroid cancers revealing generic and tumor‐specific states occurring in cancer cells and in the tumor microenvironment. In this context, cancer dedifferentiation mirrored organoid maturation through ordered thyroid marker gain/loss ...
Adrien Tourneur   +11 more
wiley   +1 more source

Inhibition of cyclin‐dependent kinases 12/13 using CT7439 as a treatment for colorectal cancer with CDK12 upregulation

open access: yesMolecular Oncology, EarlyView.
The proposed mechanism of action for the CDK12/13 inhibitor and cyclin K degrader, CT7439. CDK12/13 inhibition interrupts transcription elongation, leading to increased DNA damage that results in cell death. This agent is a potentially novel treatment option for patients with colorectal cancer. Created in BioRender. Cyclin‐dependent kinase (CDK) 12 and
Wylie K. Watlington   +10 more
wiley   +1 more source

In vitro and in silico modelling of ROS1‐positive non‐small cell lung cancer reveals fusion‐dependent tyrosine kinase inhibitor responses

open access: yesMolecular Oncology, EarlyView.
Drug resistance limits treatment success in a subset of lung cancers driven by ROS1 gene alterations. Using patient‐derived cells and computer simulations, we studied three key mutations and how they affect five targeted drugs. The mutations reduced drug effectiveness in different ways by altering protein structure and behavior.
Farhan Ul Haq   +8 more
wiley   +1 more source

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