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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 ...
Targeting of Ras-mediated FGF signaling suppresses Pten-deficient skin tumor.
(2016-11)
Deficiency in PTEN (phosphatase and tensin homolog deleted on chromosome 10) is the underlying cause of PTEN hamartoma tumor syndrome and a wide variety of human cancers. In skin epidermis, we have previously identified ...
LKB1 is required for hepatic bile acid transport and canalicular membrane integrity in mice.
(2011-02)
LKB1 is a 'master' protein kinase implicated in the regulation of metabolism, cell proliferation, cell polarity and tumorigenesis. However, the long-term role of LKB1 in hepatic function is unknown. In the present study, ...
Targeting acute myeloid leukemia by drug-induced c-MYB degradation.
(2018-04)
Despite advances in our understanding of the molecular basis for particular subtypes of acute myeloid leukemia (AML), effective therapy remains a challenge for many individuals suffering from this disease. A significant ...
Analysis of Breast Cancer Cell Invasion Using an Organotypic Culture System.
(2017-01)
Metastasis is the main cause of cancer patient mortality. Local tumor invasion is a key step in metastatic dissemination whereby cancer cells dislodge from primary tumors, migrate through the peritumoral stroma and reach ...
Oncogenic RAS Signaling Promotes Tumor Immunoresistance by Stabilizing PD-L1 mRNA.
(2017-12-12)
The immunosuppressive protein PD-L1 is upregulated in many cancers and contributes to evasion of the host immune system. The relative importance of the tumor microenvironment and cancer cell-intrinsic signaling in the ...
Mesenchymal Cancer Cell-Stroma Crosstalk Promotes Niche Activation, Epithelial Reversion, and Metastatic Colonization.
(2015-12-06)
During metastatic colonization, tumor cells must establish a favorable microenvironment or niche that will sustain their growth. However, both the temporal and molecular details of this process remain poorly understood. ...
Targeting DNA Repair in Cancer: Beyond PARP Inhibitors.
(2017-01)
Germline aberrations in critical DNA-repair and DNA damage-response (DDR) genes cause cancer predisposition, whereas various tumors harbor somatic mutations causing defective DDR/DNA repair. The concept of synthetic lethality ...
Combining DNA damaging therapeutics with immunotherapy: more haste, less speed.
(2018-02)
The idea that chemotherapy can be used in combination with immunotherapy may seem somewhat counterproductive, as it can theoretically eliminate the immune cells needed for antitumour immunity. However, much preclinical ...
Integration of RNAi and Small Molecule Screens to Identify Targets for Drug Development.
(2019-01)
Cellular models for siRNA and small molecule high-throughput screening have been widely used in the last decade to identify targets for drug discovery. As an example, we present a twofold readout approach based on cell ...