Loss of CYLD accelerates melanoma development and progression in the Tg(Grm1) melanoma mouse model

de Jel MM, Schott M, Lamm S, Neuhuber W, Kuphal S, Boßerhoff AK (2019)

Publication Type: Journal article

Publication year: 2019

Journal

Oncogenesis Nature Publishing Group

Book Volume: 8

Article Number: 56

Journal Issue: 10

DOI: 10.1038/s41389-019-0169-4

Abstract

The deubiquitinase cylindromatosis (CYLD) is a well-known tumor suppressor, found to be down regulated in many cancer types including breast cancer, colon carcinoma and malignant melanoma. CYLD is suppressed in human melanoma cells by the transcriptional repressor SNAIL1 leading to an increase of their proliferative, invasive and migratory potential. To gain additional insights into the distinct function of this tumor suppressor gene a new mouse model Tg(Grm1)Cyld−/− was generated. Herewith, we demonstrate that Cyld-deficiency leads to earlier melanoma onset and accelerated tumor growth and metastasis in the GRM1 melanoma mouse model. First, RNA sequencing data revealed a potential role of CYLD in the regulation of genes involved in proliferation, migration and angiogenesis. Experiments using cell lines generated from both primary and metastatic melanoma tissue of Tg(Grm1) Cyld−/− and Tg(Grm1) Cyld+/+ mice confirmed that loss of CYLD enhances the proliferative and migratory potential, as well as the clonogenicity in vitro. Moreover, we could show that Cyld-knockout leads to increased vasculogenic mimicry and enhanced (lymph-) angiogenesis shown by tube formation assays, immunohistochemistry and mRNA expression analyses. In summary, our findings reveal new functional aspects of CYLD in the process of (lymph-) angiogenesis and demonstrate its importance in the early process of melanoma progression.

Authors with CRIS profile

Miriam Martha de Jel Lehrstuhl für Biochemie und Molekulare Medizin Mandy Schott Lehrstuhl für Biochemie und Molekulare Medizin Winfried Neuhuber Lehrstuhl für Mikroskopische Anatomie und Molekulare Zellbiologie Silke Kuphal Lehrstuhl für Biochemie und Molekulare Medizin Anja Katrin Boßerhoff Lehrstuhl für Biochemie und Molekulare Medizin

How to cite

APA:

de Jel, M.M., Schott, M., Lamm, S., Neuhuber, W., Kuphal, S., & Boßerhoff, A.K. (2019). Loss of CYLD accelerates melanoma development and progression in the Tg(Grm1) melanoma mouse model. Oncogenesis, 8(10). https://doi.org/10.1038/s41389-019-0169-4

MLA:

de Jel, Miriam Martha, et al. "Loss of CYLD accelerates melanoma development and progression in the Tg(Grm1) melanoma mouse model." Oncogenesis 8.10 (2019).

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