Tyrosinase suppresses vasculogenic mimicry in human melanoma cells.
CRISPR/Cas9
IBMX
arbutin
melanogenesis
melanoma
tyrosinase
vasculogenic mimicry
α-MSH
Journal
Oncology letters
ISSN: 1792-1082
Titre abrégé: Oncol Lett
Pays: Greece
ID NLM: 101531236
Informations de publication
Date de publication:
May 2022
May 2022
Historique:
received:
01
02
2022
accepted:
15
03
2022
entrez:
2
5
2022
pubmed:
3
5
2022
medline:
3
5
2022
Statut:
ppublish
Résumé
Melanoma is a type of skin cancer that derives from melanocytes; this tumor is highly metastatic and causes poor clinical outcomes in patients. Vasculogenic mimicry (VM), a vascular-like network that is formed by tumor cells instead of endothelial cells, promotes the growth and metastasis of tumors by providing tumors with oxygen- and nutrient-containing blood. VM correlates with a poor prognosis in patients with melanoma, but the melanoma-specific mechanisms of VM are unknown. The present study revealed that treatment with the melanogenesis stimulators 3-isobutyl 1-methylxanthine (IBMX) and α-melanocyte-stimulating hormone (α-MSH) significantly inhibited VM in MNT-1 human pigmented melanoma cells. Tyrosinase (TYR), an essential enzyme in melanin production, was upregulated on treatment with α-MSH and IBMX, prompting an examination of the association between TYR and VM. A TYR inhibitor, arbutin, promoted VM in melanoma cells. Furthermore, CRISPR/Cas9-mediated knockout (KO) of TYR increased VM by melanoma cells. Notably, even in non-pigmented melanoma cells, TYR attenuated VM. Although re-expression of wild-type TYR suppressed VM in TYR-KO cells, T373K TYR, a frequently detected mutation in individuals with albinism, failed to inhibit VM. Overall, these results demonstrated that TYR negatively regulates VM, providing novel insights into the antioncogenic function of TYR in melanomas.
Identifiants
pubmed: 35496574
doi: 10.3892/ol.2022.13289
pii: OL-23-05-13289
pmc: PMC9019664
doi:
Types de publication
Journal Article
Langues
eng
Pagination
169Informations de copyright
Copyright: © Kamo et al.
Déclaration de conflit d'intérêts
The authors declare that they have no competing interests.
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