TYRO3 as a molecular target for growth inhibition and apoptosis induction in bladder cancer
| Autor: | F. Radvanyi, Nicolas Stransky, Vanessa Duong, Yves Allory, Isabelle Bernard-Pierrot, Elodie Chapeaublanc, Pascale Maillé, Hélène Neyret-Kahn, Marion Dorland-Galliot, Florent Dufour, Narjesse Karboul, Thierry Menguy, Hélène Haegel, Aura Moreno-Vega, Linda Silina, Clémentine Krucker |
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| Přispěvatelé: | Université Paris sciences et lettres (PSL), Compartimentation et dynamique cellulaires (CDC), Institut Curie [Paris]-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Département de pathologie [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12) |
| Jazyk: | angličtina |
| Předmět: |
Cancer Research
Cell Survival Receptor expression Gene Expression Apoptosis [SDV.CAN]Life Sciences [q-bio]/Cancer Hylobatidae In Vitro Techniques [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology Article Receptor tyrosine kinase Mice 03 medical and health sciences chemistry.chemical_compound Targeted therapies 0302 clinical medicine Cell Line Tumor Proto-Oncogene Proteins [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry Molecular Biology/Genomics [q-bio.GN] Animals Humans Medicine Neoplasm Invasiveness Molecular Targeted Therapy Urothelium Carcinoma Transitional Cell Bladder cancer c-Mer Tyrosine Kinase biology business.industry Immunochemistry Receptor Protein-Tyrosine Kinases Cancer Muscle Smooth MERTK medicine.disease Axl Receptor Tyrosine Kinase 3. Good health Urinary Bladder Neoplasms Oncology chemistry 030220 oncology & carcinogenesis biology.protein Cancer research Growth inhibition business Neoplasm Transplantation TYRO3 |
| Zdroj: | British Journal of Cancer British Journal of Cancer, Cancer Research UK, 2019, 120 (5), pp.555-564. ⟨10.1038/s41416-019-0397-6⟩ |
| ISSN: | 1532-1827 0007-0920 |
| DOI: | 10.1038/s41416-019-0397-6 |
| Popis: | International audience; BACKGROUND: Muscle-invasive bladder cancer (MIBC) is an aggressive neoplasm with poor prognosis, lacking effective therapeutic targets. Oncogenic dependency on members of the TAM tyrosine kinase receptor family (TYRO3, AXL, MERTK) has been reported in several cancer types, but their role in bladder cancer has never been explored.METHODS: TAM receptor expression was evaluated in two series of human bladder tumours by gene expression (TCGA and CIT series), immunohistochemistry and western blotting analyses (CIT series). The role of the different TAM receptors was assessed by loss-of-function experiments and pharmaceutical inhibition in vitro and in vivo.RESULTS: We reported a significantly higher expression of TYRO3, but not AXL or MERTK, in both non-MIBCs and MIBCs, compared to normal urothelium. Loss-of-function experiments identified a TYRO3-dependency of bladder carcinoma-derived cells both in vitro and in a mouse xenograft model, whereas AXL and MERTK depletion had only a minor impact on cell viability. Accordingly, TYRO3-dependent bladder tumour cells were sensitive to pharmacological treatment with two pan-TAM inhibitors. Finally, growth inhibition upon TYRO3 depletion relies on cell cycle inhibition and apoptosis associated with induction of tumour-suppressive signals.CONCLUSIONS: Our results provide a preclinical proof of concept for TYRO3 as a potential therapeutic target in bladder cancer. |
| Databáze: | OpenAIRE |
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