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Communication

Road to Metastasis: The TWEAK Pathway as a Discriminant between Metastasizing and Non-Metastasizing Thick Melanomas

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Department of Dermatology, University Hospitals Leuven, 3000 Leuven, Belgium
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Department of Imaging and Pathology, Translational Cell and Tissue Research, University Hospitals Leuven, 3000 Leuven, Belgium
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Department of Pathology and Laboratory Medicine, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, Poland
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Diagnostic Hematology Department, Institute of Hematology and Transfusion Medicine, 02-776 Warsaw, Poland
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Department of Soft Tissue/Bone Sarcoma and Melanoma, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, Poland
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Melanoma Institute Australia, The University of Sydney, Sydney, NSW 2000, Australia
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Faculty of Medicine and Health, Sydney Medical School, The University of Sydney, Sydney, NSW 2000, Australia
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Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Sydney, NSW 2000, Australia
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NSW Health Pathology, Sydney, NSW 2000, Australia
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Charles Perkins Centre, The University of Sydney, Sydney, NSW 2000, Australia
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Department of Melanoma and Surgical Oncology, Royal Prince Alfred Hospital, Sydney, NSW 2000, Australia
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Institute of Medical Research at St James’s, University of Leeds, Leeds LS2 9JT, UK
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Department of Surgical Oncology, University Hospitals Leuven, 3000 Leuven, Belgium
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Department of General Medical Oncology, University Hospitals Leuven, 3000 Leuven, Belgium
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Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Clinical and Epidemiological Virology, Katholieke Universiteit Leuven, 3000 Leuven, Belgium
*
Authors to whom correspondence should be addressed.
Academic Editor: Daniela Mihic-Probst
Int. J. Mol. Sci. 2021, 22(19), 10568; https://doi.org/10.3390/ijms221910568
Received: 29 August 2021 / Revised: 20 September 2021 / Accepted: 25 September 2021 / Published: 29 September 2021
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. View Full-Text
Keywords: melanoma; thick Breslow; TWEAK pathway melanoma; thick Breslow; TWEAK pathway
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MDPI and ACS Style

Güvenç, C.; Antoranz, A.; Szumera-Ciećkiewicz, A.; Teterycz, P.P.; Rutkowski, P.R.; Rawson, R.V.; Scolyer, R.A.; Thompson, J.F.; Newton-Bishop, J.; Stas, M.; Boecxstaens, V.; Bechter, O.; Vercauteren, J.; Garmyn, M.; van den Oord, J.; Bosisio, F.M. Road to Metastasis: The TWEAK Pathway as a Discriminant between Metastasizing and Non-Metastasizing Thick Melanomas. Int. J. Mol. Sci. 2021, 22, 10568. https://doi.org/10.3390/ijms221910568

AMA Style

Güvenç C, Antoranz A, Szumera-Ciećkiewicz A, Teterycz PP, Rutkowski PR, Rawson RV, Scolyer RA, Thompson JF, Newton-Bishop J, Stas M, Boecxstaens V, Bechter O, Vercauteren J, Garmyn M, van den Oord J, Bosisio FM. Road to Metastasis: The TWEAK Pathway as a Discriminant between Metastasizing and Non-Metastasizing Thick Melanomas. International Journal of Molecular Sciences. 2021; 22(19):10568. https://doi.org/10.3390/ijms221910568

Chicago/Turabian Style

Güvenç, Canan, Asier Antoranz, Anna Szumera-Ciećkiewicz, Pawel P. Teterycz, Piotr R. Rutkowski, Robert V. Rawson, Richard A. Scolyer, John F. Thompson, Julia Newton-Bishop, Marguerite Stas, Veerle Boecxstaens, Oliver Bechter, Jurgen Vercauteren, Marjan Garmyn, Joost van den Oord, and Francesca M. Bosisio. 2021. "Road to Metastasis: The TWEAK Pathway as a Discriminant between Metastasizing and Non-Metastasizing Thick Melanomas" International Journal of Molecular Sciences 22, no. 19: 10568. https://doi.org/10.3390/ijms221910568

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