Cutaneous melanoma is a complex disorder characterized by an elevated degree of heterogeneity, features that place it among the most aggressive types of cancer.,Although significant progress was recorded in both the understanding of melanoma biology and genetics, and in therapeutic approaches, this malignancy still represents a major problem worldwide due to its high incidence and the lack of a curative treatment for advanced stages.,This review offers a survey of the most recent information available regarding the melanoma epidemiology, etiology, and genetic profile.,Also discussed was the topic of cutaneous melanoma murine models outlining the role of these models in understanding the molecular pathways involved in melanoma initiation, progression, and metastasis.
Fascin is a F-actin bundling protein and its overexpression is correlated with poor prognosis and increases metastatic potential in a number of cancers.,But underlying function and mechanism of fascin on tumorigenesis in melanoma remain elusive.,The melanoma cell lines WM793 and WM39 were employed for the soft agar and sphere formation assay.,Quantitative RT-PCR and Western blot were performed for identifying the gene expression at mRNA and protein levels, respectively.,Co-IP and in vitro GST pulldown experiments were used to test the interaction between fascin and MST2.,Fascin regulates tumorigenesis and cancer cell stemness in melanoma through inhibition of the Hippo pathway kinase MST2 and the activation of transcription factor TAZ.,Our data showed that fascin interacts with the kinase domain of MST2 to inhibit its homodimer formation and kinase activity.,Depletion of fascin led to increase of p-LATS level and decrease of TAZ, but not YAP.,We also demonstrated that fascin regulates melanoma tumorigenesis independent of its actin-bundling activity.,Fascin is a new regulator of the MST2-LATS-TAZ pathway and plays a critical role in melanoma tumorigenesis.,Inhibition of fascin reduces melanoma tumorigenesis and stemness, and thus fascin could be a potential therapeutic target for this malignancy.,The online version of this article (10.1186/s12964-018-0250-1) contains supplementary material, which is available to authorized users.