A5082422627- Pancreatic and Hepatic Oncology Research
- Histone Deacetylase Inhibitors Research
- Cell Adhesion Molecules Research
- Cancer Cells and Metastasis
- Phagocytosis and Immune Regulation
- Cancer Immunotherapy and Biomarkers
- Cancer, Hypoxia, and Metabolism
- Bone and Dental Protein Studies
- Proteoglycans and glycosaminoglycans research
- Epigenetics and DNA Methylation
- Cancer Research and Treatments
- Glycosylation and Glycoproteins Research
- Caveolin-1 and cellular processes
- Cancer-related Molecular Pathways
- Neuroblastoma Research and Treatments
- TGF-β signaling in diseases
- Nuclear Receptors and Signaling
- RNA modifications and cancer
- Cancer Mechanisms and Therapy
- Pluripotent Stem Cells Research
- Cancer-related gene regulation
- Liver Diseases and Immunity
- Inflammation biomarkers and pathways
- Parasitic infections in humans and animals
- Polysaccharides and Plant Cell Walls
BerGenBio (Norway)
2016-2024
University of California, Los Angeles
2019-2023
UCLA Health
2019
The University of Texas Southwestern Medical Center
2012-2018
Haukeland University Hospital
2017-2018
Inserm
2017-2018
Institut Gustave Roussy
2017-2018
Southwestern Medical Center
2012-2018
Université Paris-Sud
2017-2018
University of Bergen
2017-2018
The extracellular matrix (ECM), a principal component of pancreatic ductal adenocarcinoma (PDA), is rich in fibrillar collagens that facilitate tumor cell survival and chemoresistance. Discoidin domain receptor 1 (DDR1) tyrosine kinase specifically binds has been implicated promoting proliferation, migration, adhesion, ECM remodeling, response to growth factors. We found collagen-induced activation DDR1 stimulated protumorigenic signaling through protein 2 (PYK2) pseudopodium-enriched...
Abstract There is growing evidence that antiangiogenic therapy stimulates cancer cell invasion and metastasis. However, the underlying molecular mechanisms responsible for these changes have not been fully defined. Here, we report anti-VEGF promotes local metastasis by inducing collagen signaling in cells. We show chronic VEGF inhibition a genetically engineered mouse model of pancreatic ductal adenocarcinoma (PDA) induces hypoxia, less differentiated mesenchymal-like tumor phenotype, TGF-β...
Therapy-induced hypoxia drives changes in the tumor microenvironment that contribute to poor response therapy. Hypoxia is capable of driving expression and/or activation specific signaling cascades (e.g., c-Met, Axl, CTGF), recruitment promoting immune cells, and induction cell survival pathways including autophagy (Phan et al., 2013; Hu 2012; Ye 2010). We have recently shown anti-VEGF therapy-induced can result extracellular matrix aggressiveness tumors post therapy (Aguilera 2014)....
Tumor cell subpopulations can either compete with each other for nutrients and physical space within the tumor niche, or co-operate enhanced survival, replicative metastatic capacities. Recently, we have described co-operative interactions between two clonal derived from PC-3 prostate cancer line, in which invasiveness of a stem (CSC)-enriched subpopulation (PC-3M, M) is by non-CSC (PC-3S, S), resulting their accelerated dissemination. M S secretomes were compared SILAC (Stable Isotope...
Discoidin domain receptor 1 (DDR1), a tyrosine kinase that utilizes collagen as ligand, is key molecule in the progression of solid tumors it regulates interaction cancer cells with tumor stroma. However, clinical relevance DDR1 expression gastric carcinoma yet to be investigated. Here, we assessed role mediating aggressive phenotype and its potential therapeutic target.We conducted immunohistochemistry using tissue microarray 202 specimens. We examined effect collagen-induced activation on...
TPS43 Background: Activation of the receptor tyrosine kinase AXL has a profound suppressive effect on innate immune system. is overexpressed multiple cell types in tumour microenvironment including dendritic cells, NK cells and tumour-associated macrophages. signalling supports escape by downregulating activity, modulating efferocytosis as well favouring an immunosuppressive chemokine profile M-MDSC expansion. prevalent tumours resistant to anti-PD-1 therapy (Hugo, 2016). Axl expression...
WNT signaling promotes pancreatic ductal adenocarcinoma (PDAC) through diverse effects on proliferation, differentiation, survival, and stemness. A subset of PDAC with inactivating mutations in ring finger protein 43 (RNF43) show growth dependency autocrine ligand are susceptible to agents that block acylation by Porcupine O-acyltransferase, which is required for proper processing secretion. For this study, global transcriptomic, proteomic, metabolomic analyses were performed explore the...
Age is the major risk factor in most carcinomas, yet little known about how proteomes change with age any human epithelium. We present comprehensive comprised of >9,000 total proteins and >15,000 phosphopeptides from normal primary mammary epithelia at lineage resolution ten women ranging 19 to 68 years. Data were quality controlled results biologically validated cell-based assays. Age-dependent protein signatures identified using differential expression analyses weighted co-expression...
Abstract The AXL receptor tyrosine kinase is associated with poor overall survival in a wide spectrum of cancers including lung and breast adenocarcinomas. signaling an important regulator tumor plasticity related to epithelial-to-mesenchymal transition (EMT) stem cell traits that drive metastasis drug resistance. Signaling via also key suppressor the anti-tumor innate immune response, expressed on several cells microenvironment natural killer (NK) tumor-associated macrophages. Hence resides...
Abstract The AXL receptor tyrosine kinase is associated with poor overall survival in a wide spectrum of cancers. signaling important for tumor cell plasticity related to epithelial-to-mesenchymal transition (EMT), immune escape and intrinsic resistance cytotoxic lymphocytes. expressed on several cells the microenvironment, including natural killer (NK) cells, dendritic subset tumor-associated myeloid cells. enhances secretion immune-suppressive cytokines from innate that limit antitumor...
The receptor tyrosine kinase AXL promotes tumor progression, metastasis, and therapy resistance through the induction of epithelial-mesenchymal transition (EMT). Here, we found that activation resulted in phosphorylation TANK-binding 1 (TBK1) downstream AKT3 Snail, a transcription factor critical for EMT. Mechanistically, showed TBK1 directly bound to phosphorylated manner dependent on multiprotein complex mTORC1. Upon activation, interacted with promoted nuclear accumulation which led...
Abstract Age is the major risk factor in most carcinomas, yet, little known about specific reasons aging increases cancer susceptibility. In mammary gland, luminal epithelial cells rank high as putative breast cell of origin. Dysregulation keratin intermediate filament proteins exemplifies a hallmark age-dependent change cells, which implicates mechanical states unique to susceptible cells. We implemented mechano-node-pore sensing (mechano-NPS), multi-parametric single-cell analysis that...
Abstract The extracellular matrix (ECM) is a principal component of pancreatic ductal adenocarcinoma (PDA), which rich in fibrillar collagens, and provides structural support that facilitates tumor cell survival chemoresistance. Collagen expression deposition complex process orchestrated part by the matricellular protein SPARC. SPARC human patients with PDA correlates improved chemoresponse; however, this mechanism unclear. We propose controls collagen binding to surface reduces...
Abstract The AXL receptor tyrosine kinase is expressed by several tumor types and associated with poor overall survival in patients. signaling an important regulator of cell plasticity related to epithelial-to-mesenchymal transition (EMT) stem traits that drive metastasis, drug resistance immune evasion. also on cells the inflammatory microenvironment including natural killer (NK) cells, dendritic tumor-associated macrophages. Signaling via a key suppressor anti-tumor innate response. Hence,...
Abstract Background. The AXL receptor tyrosine kinase is associated with poor overall survival in breast cancer. signaling an important regulator of tumor plasticity related to epithelial-to-mesenchymal transition (EMT) and stem cell traits that drive metastasis drug resistance. Upregulation has been reduced response anti-PD-1 therapy. Signaling via also a key suppressor the anti-tumor innate immune response, expressed on several cells microenvironment. Hence contributes uniquely both...
Abstract Epithelial-to-mesenchymal transition (EMT) contributes to tumor cell survival, immune evasion, migration, invasion, and therapy resistance. Across human cancer, tumors that are high grade, poorly differentiated, have undergone EMT carry a worse prognosis with higher likelihood of metastasis. AXL, receptor tyrosine kinase, drives is implicated in progression, metastasis, resistance multiple cancer types including pancreatic breast cancer. TANK-binding kinase 1 (TBK1) central...
<p>PDF file - 2694K, Supplementary Figure 1: Characterization of tumor growth in KIC mice (LSL-KrasG12D; Cdkn2alox/lox; p48Cre). 2: Liver metastatic burden mice. 3: Level hypoxia, collagen I, Hif1alpha, and Hexokinase II tumors from treated with mcr84 or plus Gem. 4: Anti-TGFbeta inhibits mcr84-induced deposition. 5: PDA cells express receptors Sparc. 6: Peak1 activation by is sensitive to Ddr1 blockade.</p>
<p>PDF file - 2694K, Supplementary Figure 1: Characterization of tumor growth in KIC mice (LSL-KrasG12D; Cdkn2alox/lox; p48Cre). 2: Liver metastatic burden mice. 3: Level hypoxia, collagen I, Hif1alpha, and Hexokinase II tumors from treated with mcr84 or plus Gem. 4: Anti-TGFbeta inhibits mcr84-induced deposition. 5: PDA cells express receptors Sparc. 6: Peak1 activation by is sensitive to Ddr1 blockade.</p>