BackgroundFascin 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.MethodsThe 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.ResultsFascin 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.ConclusionsFascin 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.Electronic supplementary materialThe online version of this article (10.1186/s12964-018-0250-1) contains supplementary material, which is available to authorized users.

STIM1-and Orai1-mediated store-operated Ca 2+ entry (SOCE) constitutes the major Ca 2+ influx in almost all electrically nonexcitable cells. However, little is known about the spatiotemporal organization at the elementary level. Here, we developed Orai1-tethered or palmitoylated biosensor GCaMP6f to report subplasmalemmal Ca 2+ signals. We visualized spontaneous discrete and long-lasting transients ('Ca 2+ glows') arising from STIM1-Orai1 in invading melanoma cells. Ca 2+ glows occurred preferentially in single invadopodia and at sites near the cell periphery under resting conditions. Re-addition of external Ca 2+ after store depletion elicited spatially synchronous Ca 2+ glows, followed by high-rate discharge of asynchronous local events. Knockout of STIM1 or expression of the dominant-negative Orai1-E106A mutant markedly decreased Ca 2+ glow frequency, diminished global SOCE and attenuated invadopodial formation. Functionally, invadopodial Ca 2+ glows provided high Ca 2+ microdomains to locally activate Ca 2+ /calmodulin-dependent Pyk2 (also known as PTK2B), which initiates the SOCE-Pyk2-Src signaling cascade required for invasion. Overall, the discovery of elemental Ca 2+ signals of SOCE not only unveils a previously unappreciated gating mode of STIM1-Orai1 channels in situ, but also underscores a critical role of the spatiotemporal dynamics of SOCE in orchestrating complex cell behaviors such as invasion.This article has an associated First Person interview with the first author of the paper.

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