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Road to Metastasis: The TWEAK Pathway as a Discriminant between Metastasizing and Non-Metastasizing Thick Melanomas.
Güvenç, Canan; Antoranz, Asier; Szumera-Cieckiewicz, Anna; Teterycz, Pawel P; Rutkowski, Piotr R; Rawson, Robert V; Scolyer, Richard A; Thompson, John F; Newton-Bishop, Julia; Stas, Marguerite; Boecxstaens, Veerle; Bechter, Oliver; Vercauteren, Jurgen; Garmyn, Marjan; van den Oord, Joost; Bosisio, Francesca Maria.
Afiliação
  • Güvenç C; Department of Dermatology, University Hospitals Leuven, 3000 Leuven, Belgium.
  • Antoranz A; Department of Imaging and Pathology, Translational Cell and Tissue Research, University Hospitals Leuven, 3000 Leuven, Belgium.
  • Szumera-Cieckiewicz A; Department of Pathology and Laboratory Medicine, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, Poland.
  • Teterycz PP; Diagnostic Hematology Department, Institute of Hematology and Transfusion Medicine, 02-776 Warsaw, Poland.
  • Rutkowski PR; Department of Soft Tissue/Bone Sarcoma and Melanoma, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, Poland.
  • Rawson RV; Department of Soft Tissue/Bone Sarcoma and Melanoma, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, Poland.
  • Scolyer RA; Melanoma Institute Australia, The University of Sydney, Sydney, NSW 2000, Australia.
  • Thompson JF; Faculty of Medicine and Health, Sydney Medical School, The University of Sydney, Sydney, NSW 2000, Australia.
  • Newton-Bishop J; Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Sydney, NSW 2000, Australia.
  • Stas M; NSW Health Pathology, Sydney, NSW 2000, Australia.
  • Boecxstaens V; Melanoma Institute Australia, The University of Sydney, Sydney, NSW 2000, Australia.
  • Bechter O; Faculty of Medicine and Health, Sydney Medical School, The University of Sydney, Sydney, NSW 2000, Australia.
  • Vercauteren J; Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Sydney, NSW 2000, Australia.
  • Garmyn M; NSW Health Pathology, Sydney, NSW 2000, Australia.
  • van den Oord J; Charles Perkins Centre, The University of Sydney, Sydney, NSW 2000, Australia.
  • Bosisio FM; Melanoma Institute Australia, The University of Sydney, Sydney, NSW 2000, Australia.
Int J Mol Sci ; 22(19)2021 Sep 29.
Article em En | MEDLINE | ID: mdl-34638912
ABSTRACT
Cutaneous melanoma (CM) is the most aggressive form of skin cancer, and its worldwide incidence is rapidly increasing. Early stages can be successfully treated by surgery, but once metastasis has occurred, the prognosis is poor. However, some 5-10% of thick (≥2 mm) melanomas do not follow this scenario and run an unpredictable course. Little is known about the factors that contribute to metastasis in some patient with thick melanomas and the lack thereof in thick melanoma patients who never develop metastatic disease. We were therefore interested to study differential gene expression and pathway analysis and compare non-metastatic and metastatic thick melanomas. We found that the TNF-like weak inducer of apoptosis (TWEAK) pathway was upregulated in thick non-metastasizing melanomas. MAP3K14 (NIK1), BIRC2 (cIAP1), RIPK1, CASP7, CASP8, and TNF play an important role in inhibiting proliferation and invasion of tumor cells via the activation of the non-canonical NF-κB signaling pathway. In particular, this pathway sensitizes melanoma cells to TNF-alpha and activates the apoptosis module of the TWEAK pathway in thick non-metastasizing melanomas. Hence, our study suggests a potential role of the TWEAK pathway in inhibiting thick melanoma from metastasis. Exploitation of these genes and the pathway they control may open future therapeutic avenues.
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Texto completo: 1 Bases de dados: MEDLINE Assunto principal: Neoplasias Cutâneas / Transdução de Sinais / Regulação Neoplásica da Expressão Gênica / Perfilação da Expressão Gênica / Citocina TWEAK / Melanoma Tipo de estudo: Etiology_studies / Incidence_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Limite: Adult / Female / Humans / Male / Middle aged Idioma: En Revista: Int J Mol Sci Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Bélgica

Texto completo: 1 Bases de dados: MEDLINE Assunto principal: Neoplasias Cutâneas / Transdução de Sinais / Regulação Neoplásica da Expressão Gênica / Perfilação da Expressão Gênica / Citocina TWEAK / Melanoma Tipo de estudo: Etiology_studies / Incidence_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Limite: Adult / Female / Humans / Male / Middle aged Idioma: En Revista: Int J Mol Sci Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Bélgica