Browsing Molecular Pathology by author "Downward, Julian David Harry"
Now showing items 1-18 of 18
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Autophagy inhibition specifically promotes epithelial-mesenchymal transition and invasion in RAS-mutated cancer cells.
Wang, Y; Xiong, H; Liu, D; Hill, C; Ertay, A; et al. (2019-05)Macroautophagy/autophagy inhibition is a novel anticancer therapeutic strategy, especially for tumors driven by mutant RAS. Here, we demonstrate that autophagy inhibition in RAS-mutated cells induces epithelial-mesenchymal ... -
Autophagy inhibition-mediated epithelial-mesenchymal transition augments local myofibroblast differentiation in pulmonary fibrosis.
Hill, C; Li, J; Liu, D; Conforti, F; Brereton, CJ; et al. (2019-08-07)Idiopathic pulmonary fibrosis (IPF), the prototypic progressive fibrotic interstitial lung disease, is thought to be a consequence of repetitive micro-injuries to an ageing, susceptible alveolar epithelium. Ageing is a ... -
Clinical impact of subclonal EGFR T790M mutations in advanced-stage EGFR-mutant non-small-cell lung cancers.
Vaclova, T; Grazini, U; Ward, L; O'Neill, D; Markovets, A; et al. (2021-03-19)Advanced non-small-cell lung cancer (NSCLC) patients with EGFR T790M-positive tumours benefit from osimertinib, an epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI). Here we show that the size of the ... -
Combined targeting of G protein-coupled receptor and EGF receptor signaling overcomes resistance to PI3K pathway inhibitors in PTEN-null triple negative breast cancer.
Zecchin, D; Moore, C; Michailidis, F; Horswell, S; Rana, S; et al. (2020-08)Triple-negative breast cancer (TNBC) has poorer prognosis compared to other types of breast cancers due to the lack of effective therapies and markers for patient stratification. Loss of PTEN tumor suppressor gene expression ... -
Decreased glutathione biosynthesis contributes to EGFR T790M-driven erlotinib resistance in non-small cell lung cancer.
Li, H; Stokes, W; Chater, E; Roy, R; de Bruin, E; et al. (2016-01)Epidermal growth factor receptor (EGFR) inhibitors such as erlotinib are novel effective agents in the treatment of EGFR-driven lung cancer, but their clinical impact is often impaired by acquired drug resistance through ... -
Development of combination therapies to maximize the impact of KRAS-G12C inhibitors in lung cancer.
Molina-Arcas, M; Moore, C; Rana, S; van Maldegem, F; Mugarza, E; et al. (2019-09)KRAS represents an excellent therapeutic target in lung cancer, the most commonly mutated form of which can now be blocked using KRAS-G12C mutant-specific inhibitory trial drugs. Lung adenocarcinoma cells harboring KRAS ... -
Disruption of the Interaction of RAS with PI 3-Kinase Induces Regression of EGFR-Mutant-Driven Lung Cancer.
Murillo, MM; Rana, S; Spencer-Dene, B; Nye, E; Stamp, G; et al. (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 ... -
IGF1-mediated human embryonic stem cell self-renewal recapitulates the embryonic niche.
Wamaitha, SE; Grybel, KJ; Alanis-Lobato, G; Gerri, C; Ogushi, S; et al. (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 ... -
Inherited duplications of PPP2R3B predispose to nevi and melanoma via a C21orf91-driven proliferative phenotype.
Polubothu, S; Zecchin, D; Al-Olabi, L; Lionarons, DA; Harland, M; et al. (2021-06-18)Purpose Much of the heredity of melanoma remains unexplained. We sought predisposing germline copy-number variants using a rare disease approach.Methods Whole-genome copy-number findings in patients with melanoma predisposition ... -
Oncogenic RAS Signaling Promotes Tumor Immunoresistance by Stabilizing PD-L1 mRNA.
Coelho, MA; de Carné Trécesson, S; Rana, S; Zecchin, D; Moore, C; et al. (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 ... -
Paracrine signalling during ZEB1-mediated epithelial-mesenchymal transition augments local myofibroblast differentiation in lung fibrosis.
Yao, L; Conforti, F; Hill, C; Bell, J; Drawater, L; et al. (2019-05)The contribution of epithelial-mesenchymal transition (EMT) to human lung fibrogenesis is controversial. Here we provide evidence that ZEB1-mediated EMT in human alveolar epithelial type II (ATII) cells contributes to the ... -
RAC1P29S Induces a Mesenchymal Phenotypic Switch via Serum Response Factor to Promote Melanoma Development and Therapy Resistance.
Lionarons, DA; Hancock, DC; Rana, S; East, P; Moore, C; et al. (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 ... -
RAS signalling through PI3-Kinase controls cell migration via modulation of Reelin expression.
Castellano, E; Molina-Arcas, M; Krygowska, AA; East, P; Warne, P; et al. (2016-04-13)RAS signalling through phosphoinositide 3-kinase (PI3-Kinase) has been shown to have an essential role in tumour initiation and maintenance. RAS also regulates cell motility and tumour invasiveness, but the role of direct ... -
SGLT1 is required for the survival of triple-negative breast cancer cells via potentiation of EGFR activity.
Liu, H; Ertay, A; Peng, P; Li, J; Liu, D; et al. (2019-09)Sodium/glucose cotransporter 1 (SGLT1), an essential active glucose transport protein that helps maintain high intracellular glucose levels, was previously shown to interact with epidermal growth factor receptor (EGFR); ... -
SHOC2 phosphatase-dependent RAF dimerization mediates resistance to MEK inhibition in RAS-mutant cancers.
Jones, GG; Del Río, IB; Sari, S; Sekerim, A; Young, LC; et al. (2019-06-10)Targeted inhibition of the ERK-MAPK pathway, upregulated in a majority of human cancers, has been hindered in the clinic by drug resistance and toxicity. The MRAS-SHOC2-PP1 (SHOC2 phosphatase) complex plays a key role in ... -
Targeting of Ras-mediated FGF signaling suppresses Pten-deficient skin tumor.
Mathew, G; Hannan, A; Hertzler-Schaefer, K; Wang, F; Feng, G-S; et al. (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 ... -
Tumour-suppression function of KLF12 through regulation of anoikis.
Godin-Heymann, N; Brabetz, S; Murillo, MM; Saponaro, M; Santos, CR; et al. (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, ... -
WDHD1 is essential for the survival of PTEN-inactive triple-negative breast cancer.
Ertay, A; Liu, H; Liu, D; Peng, P; Hill, C; et al. (2020-11-21)Triple-negative breast cancer (TNBC) is the most aggressive type of breast cancer that lacks the oestrogen receptor, progesterone receptor and human epidermal growth factor receptor 2, making it difficult to target ...