RRC ID 71456
Author Kamo H, Kawahara R, Simizu S.
Title Tyrosinase suppresses vasculogenic mimicry in human melanoma cells.
Journal Oncol Lett
Abstract 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.
Volume 23(5)
Pages 169
Published 2022-5-1
DOI 10.3892/ol.2022.13289
PII OL-23-05-13289
PMID 35496574
PMC PMC9019664
IF 2.311
Human and Animal Cells SK-MEL-28(RCB1930) 293T(RCB2202)
DNA material Tyrosinase KO nickase1 vector (RDB20022) Tyrosinase KO nickase2 vector (RDB20023)