Showing papers by "Jean Paul Thiery published in 2020"
University of California, San Diego1, University of Arizona2, Ghent University3, Université libre de Bruxelles4, University of Erlangen-Nuremberg5, California Institute of Technology6, University of Sheffield7, Spanish National Research Council8, University of Basel9, University of British Columbia10, University of California, San Francisco11, Anschutz Medical Campus12, Karolinska University Hospital13, Pompeu Fabra University14, University of South Australia15, Memorial Sloan Kettering Cancer Center16, National Taiwan University17, Hebrew University of Jerusalem18, University of Texas MD Anderson Cancer Center19, Princeton University20, Northeastern University21, Washington University in St. Louis22, University College London23, Duke University24, Royal Children's Hospital25, Claude Bernard University Lyon 126, PSL Research University27, Université Paris-Saclay28, University of Pennsylvania29, Kyoto University30, University of Toulouse31, Queensland University of Technology32, Massachusetts Institute of Technology33, University of Pittsburgh34, University of Kentucky35, Kumamoto University36
TL;DR: This Consensus Statement is the outcome of a 2-year-long discussion among EMT researchers and aims to both clarify the nomenclature and provide definitions and guidelines for EMT research in future publications to reduce misunderstanding and misinterpretation of research data generated in various experimental models.
Abstract: Epithelial-mesenchymal transition (EMT) encompasses dynamic changes in cellular organization from epithelial to mesenchymal phenotypes, which leads to functional changes in cell migration and invasion. EMT occurs in a diverse range of physiological and pathological conditions and is driven by a conserved set of inducing signals, transcriptional regulators and downstream effectors. With over 5,700 publications indexed by Web of Science in 2019 alone, research on EMT is expanding rapidly. This growing interest warrants the need for a consensus among researchers when referring to and undertaking research on EMT. This Consensus Statement, mediated by 'the EMT International Association' (TEMTIA), is the outcome of a 2-year-long discussion among EMT researchers and aims to both clarify the nomenclature and provide definitions and guidelines for EMT research in future publications. We trust that these guidelines will help to reduce misunderstanding and misinterpretation of research data generated in various experimental models and to promote cross-disciplinary collaboration to identify and address key open questions in this research field. While recognizing the importance of maintaining diversity in experimental approaches and conceptual frameworks, we emphasize that lasting contributions of EMT research to increasing our understanding of developmental processes and combatting cancer and other diseases depend on the adoption of a unified terminology to describe EMT.
931 citations
TL;DR: This study shows that mechanisms of resistance to lorlatinib are diverse and complex, requiring new therapeutic strategies to tailor treatment upon disease progression, and identifies a novel bypass mechanism of resistance caused by NF2 loss-of-function mutations, conferring sensitivity to treatment with mTOR inhibitors.
Abstract: Purpose: Lorlatinib is a third-generation anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor with proven efficacy in patients with ALK-rearranged lung cancer previously treated with first- and second-generation ALK inhibitors. Beside compound mutations in the ALK kinase domain, other resistance mechanisms driving lorlatinib resistance remain unknown. We aimed to characterize the mechanisms of resistance to lorlatinib occurring in patients with ALK-rearranged lung cancer and design new therapeutic strategies in this setting. Experimental Design: Resistance mechanisms were investigated in 5 patients resistant to lorlatinib. Longitudinal tumor biopsies were studied using high-throughput next-generation sequencing. Patient-derived models were developed to characterize the acquired resistance mechanisms, and Ba/F3 cell mutants were generated to study the effect of novel ALK compound mutations. Drug combinatory strategies were evaluated in vitro and in vivo to overcome lorlatinib resistance. Results: Diverse biological mechanisms leading to lorlatinib resistance were identified. Epithelial–mesenchymal transition (EMT) mediated resistance in two patient-derived cell lines and was susceptible to dual SRC and ALK inhibition. We characterized three ALK kinase domain compound mutations occurring in patients, L1196M/D1203N, F1174L/G1202R, and C1156Y/G1269A, with differential susceptibility to ALK inhibition by lorlatinib. We identified a novel bypass mechanism of resistance caused by NF2 loss-of-function mutations, conferring sensitivity to treatment with mTOR inhibitors. Conclusions: This study shows that mechanisms of resistance to lorlatinib are diverse and complex, requiring new therapeutic strategies to tailor treatment upon disease progression.
103 citations
University of Bergen1, Haukeland University Hospital2, Université Paris-Saclay3, National University of Singapore4, University of Oslo5, University of Southern Denmark6, Odense University Hospital7, University of California, San Francisco8, University of Texas Southwestern Medical Center9, University of Auckland10
TL;DR: The results indicate that AXL signaling supports a drug- resistant persister cell phenotype through a novel autophagy-dependent mechanism and reveals a unique immunogenic effect of AXL inhibition on drug-resistant NSCLC cells.
58 citations
TL;DR: This review delineates the complex EMT networks and discusses recent studies that have used CRISPR/Cas technology to further advance the understanding of the EMT process.
Abstract: Epithelial to mesenchymal transition (EMT) is a complex plastic and reversible cellular process that has critical roles in diverse physiological and pathological phenomena. EMT is involved in embryonic development, organogenesis and tissue repair, as well as in fibrosis, cancer metastasis and drug resistance. In recent years, the ability to edit the genome using the clustered regularly interspaced palindromic repeats (CRISPR) and associated protein (Cas) system has greatly contributed to identify or validate critical genes in pathway signaling. This review delineates the complex EMT networks and discusses recent studies that have used CRISPR/Cas technology to further advance our understanding of the EMT process.
26 citations
TL;DR: The interpretation is that AXL regulates access to epithelial plasticity programs in MaSCs and, when co-opted, maintains acquired stemness in breast cancer cells.
23 citations
12 Oct 2020
TL;DR: This review will explore to what extent targeting EMP in combination with immune checkpoint inhibition represents a promising therapeutic avenue within the overarching strategy to reactivate a halting cancer-immunity cycle and establish a robust host immune response against cancer cells.
Abstract: Epithelial-mesenchymal plasticity (EMP) of cancer cells contributes to cancer cell heterogeneity, and it is well established that EMP is a critical determinant of acquired resistance to cancer treatment modalities including radiation therapy, chemotherapy, and targeted therapies. Here, we aimed to explore how EMP contributes to cancer cell camouflage, allowing an ever-changing population of cancer cells to pass under the radar of our immune system and consequently compromise the effect of immune checkpoint blockade therapies. The ultimate clinical benefit of any combination regimen is evidenced by the sum of the drug-induced alterations observed in the variety of cellular populations composing the tumor immune microenvironment. The finely-tuned molecular crosstalk between cancer and immune cells remains to be fully elucidated, particularly for the spectrum of Lotsberg et al . Cancer Drug Resist 2020;3:832-53 I http://dx.doi.org/10.20517/cdr.2020.41 Page 833 malignant cells along the epithelial to mesenchymal axis. High-dimensional single cell analyses of specimens collected in ongoing clinical studies is becoming a key contributor to our understanding of these interactions. This review will explore to what extent targeting EMP in combination with immune checkpoint inhibition represents a promising therapeutic avenue within the overarching strategy to reactivate a halting cancer-immunity cycle and establish a robust host immune response against cancer cells. Therapeutic strategies currently in clinical development will be discussed.
10 citations
TL;DR: The data suggest that these highly dynamic peptides harbor a type II β-turn located in their central part, and it is hypothesize that this structural element could explain their specific bioactivity.
4 citations
TL;DR: An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Abstract: An amendment to this paper has been published and can be accessed via a link at the top of the paper.
3 citations
TL;DR: It is shown that distinct EC repeats in the extracellular region of cadherins differentially modulate epithelial sheet integrity, cell-cell separation forces, and cell cortical tension through a Cdc42 pathway, which further differentially regulate epithelial tensile strength, ductility, and ultimately collective migration.
Abstract: Cadherins control intercellular adhesion in most metazoans. In vertebrates, intercellular adhesion differs considerably between cadherins of type-I and type-II, predominantly due to their different extracellular regions. Yet, intercellular adhesion critically depends on actomyosin contractility, in which the role of the cadherin extracellular region is unclear. Here, we dissect the roles of the Extracellular Cadherin (EC) Ig-like domains by expressing chimeric E-cadherin with E-cadherin and cadherin-7 Ig-like domains in cells naturally devoid of cadherins. Using cell-cell separation, cortical tension measurement, tissue-scale stretching and migration assays, we show that distinct EC repeats in the extracellular region of cadherins differentially modulate epithelial sheet integrity, cell-cell separation forces, and cell cortical tension through a Cdc42 pathway, which further differentially regulate epithelial tensile strength, ductility, and ultimately collective migration. Interestingly, dissipative processes rather than static adhesion energy mostly dominate cell-cell separation forces. We provide a framework for the emergence of epithelial phenotypes from cell mechanical properties dependent on EC outside-in signalling.
2 citations