Transglutaminase Type 2-MITF axis regulates phenotype switching in skin cutaneous melanoma.

Autor: Muccioli S; Department of Biology, University of Padua, Padua, Italy.; Laboratory of Translational Research, Azienda USL - IRCCS di Reggio Emilia, Reggio Emilia, Italy., Brillo V; Department of Biology, University of Padua, Padua, Italy., Varanita T; Department of Biology, University of Padua, Padua, Italy., Rossin F; Department of Biology, University of Rome 'Tor Vergata', Rome, Italy., Zaltron E; Department of Biology, University of Padua, Padua, Italy., Velle A; Department of Biology, University of Padua, Padua, Italy., Alessio G; Department of Biology, University of Padua, Padua, Italy., Angi B; Department of Biology, University of Padua, Padua, Italy., Severin F; Department of Biology, University of Padua, Padua, Italy., Tosi A; Immunology and Molecular Oncology Diagnostics, Veneto Institute of Oncology IOV-IRCCS, Padua, Italy., D'Eletto M; Department of Biology, University of Rome 'Tor Vergata', Rome, Italy., Occhigrossi L; Department of Biology, University of Rome 'Tor Vergata', Rome, Italy., Falasca L; National Institute for Infectious Diseases IRCCS 'Lazzaro Spallanzani', Rome, Italy., Checchetto V; Department of Biology, University of Padua, Padua, Italy., Ciaccio R; Department of Biology, University of Padua, Padua, Italy., Fascì A; Department of Biology, University of Padua, Padua, Italy., Chieregato L; Department of Biology, University of Padua, Padua, Italy., Rebelo AP; Department of Biology, University of Padua, Padua, Italy., Giacomello M; Department of Biology, University of Padua, Padua, Italy., Rosato A; Immunology and Molecular Oncology Diagnostics, Veneto Institute of Oncology IOV-IRCCS, Padua, Italy.; Department of Surgery, Oncology and Gastroenterology (DiSCOG), University of Padua, Padua, Italy., Szabò I; Department of Biology, University of Padua, Padua, Italy., Romualdi C; Department of Biology, University of Padua, Padua, Italy., Piacentini M; Department of Biology, University of Rome 'Tor Vergata', Rome, Italy.; National Institute for Infectious Diseases IRCCS 'Lazzaro Spallanzani', Rome, Italy., Leanza L; Department of Biology, University of Padua, Padua, Italy. luigi.leanza@unipd.it.
Jazyk: angličtina
Zdroj: Cell death & disease [Cell Death Dis] 2023 Oct 28; Vol. 14 (10), pp. 704. Date of Electronic Publication: 2023 Oct 28.
DOI: 10.1038/s41419-023-06223-y
Abstrakt: Skin cutaneous melanoma (SKCM) is the deadliest form of skin cancer due to its high heterogeneity that drives tumor aggressiveness. Melanoma plasticity consists of two distinct phenotypic states that co-exist in the tumor niche, the proliferative and the invasive, respectively associated with a high and low expression of MITF, the master regulator of melanocyte lineage. However, despite efforts, melanoma research is still far from exhaustively dissecting this phenomenon. Here, we discovered a key function of Transglutaminase Type-2 (TG2) in regulating melanogenesis by modulating MITF transcription factor expression and its transcriptional activity. Importantly, we demonstrated that TG2 expression affects melanoma invasiveness, highlighting its positive value in SKCM. These results suggest that TG2 may have implications in the regulation of the phenotype switching by promoting melanoma differentiation and impairing its metastatic potential. Our findings offer potential perspectives to unravel melanoma vulnerabilities via tuning intra-tumor heterogeneity.
(© 2023. The Author(s).)
Databáze: MEDLINE
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