Fascin induces melanoma tumorigenesis and stemness through regulating the Hippo pathway.
Fascin induces melanoma tumorigenesis and stemness through regulating the Hippo pathway.
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Fascin 通过调节 Hippo 通路诱导黑色素瘤肿瘤发生和干细胞性
DOI：
10.1186/s12964-018-0250-1
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发表时间：
2018-07-03
期刊：
影响因子：
--
通讯作者：
Sun J
中科院分区：
文献类型：
--
作者：
Kang J;Wang J;Yao Z;Hu Y;Ma S;Fan Q;Gao F;Sun Y;Sun J
Fascin是一种F-肌动蛋白捆绑蛋白，其过表达与许多癌症的不良预后相关，并增加转移潜能。Fascin在黑色素瘤发生中的作用机制尚不清楚。方法采用黑色素瘤细胞系WM 793和WM 39进行软琼脂和成球实验。采用RT-PCR和Western blot方法分别从mRNA和蛋白质水平鉴定基因表达。结果Fascin通过抑制Hippo通路激酶MST 2和激活转录因子TAZ，调控黑色素瘤的发生和肿瘤细胞的干细胞性。我们的数据表明，肌成束蛋白与MST 2的激酶结构域相互作用，以抑制其同源二聚体的形成和激酶活性。fascin的缺失导致p-LATS水平升高，TAZ水平降低，但雅普水平无明显变化。我们还表明，肌成束蛋白调节黑色素瘤的肿瘤发生独立的肌动蛋白捆绑activity.ConclusionsFascin是一个新的调节MST 2-LATS-TAZ通路，并在黑色素瘤的肿瘤发生中起着至关重要的作用。抑制肌成束蛋白可降低黑色素瘤的肿瘤发生和干性，因此肌成束蛋白可能是这种恶性肿瘤的潜在治疗靶点。
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.
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影响因子：
3.7
作者：
Ruiz de Garibay G;Herranz C;Llorente A;Boni J;Serra-Musach J;Mateo F;Aguilar H;Gómez-Baldó L;Petit A;Vidal A;Climent F;Hernández-Losa J;Cordero Á;González-Suárez E;Sánchez-Mut JV;Esteller M;Llatjós R;Varela M;López JI;García N;Extremera AI;Gumà A;Ortega R;Plà MJ;Fernández A;Pernas S;Falo C;Morilla I;Campos M;Gil M;Román A;Molina-Molina M;Ussetti P;Laporta R;Valenzuela C;Ancochea J;Xaubet A;Casanova Á;Pujana MA
通讯作者：
Pujana MA
DOI：
10.1016/j.biocel.2010.06.019
发表时间：
2010-10-01
影响因子：
4
作者：
Jayo, Asier;Parsons, Maddy
通讯作者：
Parsons, Maddy
影响因子：
3.7
作者：
Reddy P;Deguchi M;Cheng Y;Hsueh AJ
通讯作者：
Hsueh AJ
影响因子：
56.9
作者：
Hong, JH;Hwang, ES;Yaffe, MB
通讯作者：
Yaffe, MB
TAZ 促进细胞增殖和上皮间质转化，并受 hippo 通路抑制
影响因子：
5.3
作者：
Lei, Qun-Ying;Zhang, Heng;Guan, Kun-Liang
通讯作者：
Guan, Kun-Liang