Enhanced anti-melanoma efficacy of interferon alfa-2b via inhibition of Shp2

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• 作者：Hla Win-Piazza^a ; ¹ ; Valentina E. Schneeberger^a ; ^b ; Liwei Chen^a ; Daniele Pernazza^c ; Harshani R. Lawrence^c ; ^d ; Said M. Sebti^b ; ^c ; ^e ; Nicholas J. Lawrence^c ; ^e ; Jie Wu^a ; ^b ; ^c ; ^e ; ^{jerry.wu@moffitt.org}
• 关键词：Shp2 ; STAT1 ; Melanoma ; Interferon
• 刊名：Cancer Letters
• 出版年：2012
• 期刊代码：44_03043835
• 类别：med
• 出版时间：1 July, 2012
• 卷：320
• 期：1
• 页码：81-85
• 文件大小：714 K

摘要

Interferon-伪2b (IFN-伪2b) is used to treat melanoma but there is a need to improve its efficacy. IFN-伪2b signaling requires STAT1/STAT2 tyrosine phosphorylation and is subject to negative regulation by phosphatases. In this study, we determined whether inhibition of the protein tyrosine phosphatase Shp2 could enhance IFN-伪2b responses in human melanoma cells. Shp2 knockdown increased IFN-伪2b-stimulated STAT1 Tyr-701 phosphorylation and ISRE-luciferase activity even though it did not affect STAT2 Tyr-690 phosphorylation in A375 cells. In A375 tumor xenografts, Shp2 knockdown enhanced the anti-melanoma effect of IFN-伪2b. Furthermore, the Shp2 inhibitor SPI-112Me increased the IFN-伪2b-induced STAT1 activation and anti-proliferative response in A375 and SK-MEL-2 cells. These results demonstrate that inhibition of Shp2 can enhance the anti-melanoma activity of IFN-伪2b.