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Tumour-suppression function of KLF12 through regulation of anoikis.
(2016-06)
Suppression of detachment-induced cell death, known as anoikis, is an essential step for cancer metastasis to occur. We report here that expression of KLF12, a member of the Kruppel-like family of transcription factors, ...
Disruption of the Interaction of RAS with PI 3-Kinase Induces Regression of EGFR-Mutant-Driven Lung Cancer.
(2018-12)
RAS family GTPases contribute directly to the regulation of type I phosphoinositide 3-kinases (PI3Ks) via RAS-binding domains in the PI3K catalytic p110 subunits. Disruption of this domain of p110α impairs RAS-mutant-onc ...
A comprehensive model for the proliferation-quiescence decision in response to endogenous DNA damage in human cells.
(NATL ACAD SCIENCES, 2018-03-06)
Human cells that suffer mild DNA damage can enter a reversible state of growth arrest known as quiescence. This decision to temporarily exit the cell cycle is essential to prevent the propagation of mutations, and most ...
Systematic analysis of tumour cell-extracellular matrix adhesion identifies independent prognostic factors in breast cancer.
(IMPACT JOURNALS LLC, 2016-08-17)
Tumour cell-extracellular matrix (ECM) interactions are fundamental for discrete steps in breast cancer progression. In particular, cancer cell adhesion to ECM proteins present in the microenvironment is critical for ...
PARK2 Depletion Connects Energy and Oxidative Stress to PI3K/Akt Activation via PTEN S-Nitrosylation.
(CELL PRESS, 2017-03-16)
PARK2 is a gene implicated in disease states with opposing responses in cell fate determination, yet its contribution in pro-survival signaling is largely unknown. Here we show that PARK2 is altered in over a third of all ...
ATR Is a Therapeutic Target in Synovial Sarcoma.
(AMER ASSOC CANCER RESEARCH, 2017-12-15)
Synovial sarcoma (SS) is an aggressive soft-tissue malignancy characterized by expression of SS18-SSX fusions, where treatment options are limited. To identify therapeutically actionable genetic dependencies in SS, we ...
Single-Cell Dynamics Determines Response to CDK4/6 Inhibition in Triple-Negative Breast Cancer.
(AMER ASSOC CANCER RESEARCH, 2017-09-15)
Purpose: Triple-negative breast cancer (TNBC) is a heterogeneous subgroup of breast cancer that is associated with a poor prognosis. We evaluated the activity of CDK4/6 inhibitors across the TNBC subtypes and investigated ...
DNA damage during S-phase mediates the proliferation-quiescence decision in the subsequent G1 via p21 expression.
(NATURE PUBLISHING GROUP, 2017-03-20)
Following DNA damage caused by exogenous sources, such as ionizing radiation, the tumour suppressor p53 mediates cell cycle arrest via expression of the CDK inhibitor, p21. However, the role of p21 in maintaining genomic ...
ROS Dynamics Delineate Functional States of Hippocampal Neural Stem Cells and Link to Their Activity-Dependent Exit from Quiescence.
(CELL PRESS, 2021-02-04)
Cellular redox states regulate the balance between stem cell maintenance and activation. Increased levels of intracellular reactive oxygen species (ROS) are linked to proliferation and lineage specification. In contrast ...
Characterization of proteome-size scaling by integrative omics reveals mechanisms of proliferation control in cancer.
(AMER ASSOC ADVANCEMENT SCIENCE, 2023-01-25)
Almost all living cells maintain size uniformity through successive divisions. Proteins that over and underscale with size can act as rheostats, which regulate cell cycle progression. Using a multiomic strategy, we leveraged ...