Prognostic Significance of Sox4 Expression in Human Cutaneous Melanoma and Its Role in Cell Migration and Invasion
Prognostic Significance of Sox4 Expression in Human Cutaneous Melanoma and Its Role in Cell Migration and Invasion
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DOI：
10.2353/ajpath.2010.100377
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发表时间：
2010-12-01
影响因子：
6
通讯作者：
Li, Gang
中科院分区：
文献类型：
--
作者：
Jafarnejad, Seyed Mehdi;Wani, Aijaz Ahmad;Li, Gang
Sox 4转录因子参与了多种细胞过程，如胚胎发育和分化。迄今为止，已有报道Sox 4在几种人类癌症中表达失调，但其在黑色素瘤中的作用尚不清楚。我们在体内和体外探索了Sox 4在黑色素瘤发病机制中的作用。与异型增生nev 1相比，转移性黑色素瘤中Sox 4的表达显著降低，（P <005）与原发性黑色素瘤这种降低与黑色素瘤患者的疾病特异性生存率降低相关（P <001）多因素考克斯回归分析显示，Sox 4表达降低是独立的预后因素（P = 0 0 49）Sox 4基因敲除可增强黑色素瘤细胞的侵袭、迁移和应力纤维形成。当p50被敲低时，NF-κ B p50被废除。我们进一步观察到，除了NF-κ B p50转录的反向模式外，Sox 4还抑制NF-κ B p50转录。Sox 4和NF κ B B p50在黑素细胞病变不同阶段的表达我们的研究结果表明，Sox 4以NF κ B B p50依赖的方式调节黑素细胞的迁移和侵袭，并可能作为人类黑素细胞的预后标志物和潜在的治疗靶点（Am J Pathol 2010 177 2741-2752 DOI 10 2353/ajpath 2010 100377）
The Sox4 transcription factor is involved m various cellular processes such as embryonic development and differentiation Deregulated expression of Sox4 in several human cancers has been reported to date but its role in melanoma is unknown We explored the role of Sox4 in melanoma pathogenesis in vivo and in vitro Using tissue microarray we evaluated Sox4 expression in 180 melanocytic lesions and investigated its role in melanoma cell migration and invasion Sox4 expression was remarkably reduced in metastatic melanoma compared with dysplastic nev1 (P < 0 05) and primary melanoma (P < 0 01) This reduction was correlated with a poorer disease specific survival of melanoma patients (P = 0 039) Multivariate Cox regression analysis revealed that reduced Sox4 expression is an independent prognostic factor (P = 0 049) Knockdown of Sox4 enhanced melanoma cell invasion migration and stress fiber formation The increased migration and invasion on Sox4 knockdown depends on the presence of nuclear factor (NF) kappa B p50 and is abrogated when p50 is knocked down We further observed inhibition of NF kappa B p50 transcription by Sox4 in addition to a reverse pattern of expression of Sox4 and NF kappa B p50 in different stages of melanocytic lesions Our results suggest that Sox4 regulates melanoma cell migration and invasion in an NF kappa B p50 dependent manner and may serve as a prognostic marker and potential therapeutic target for human melanoma (Am J Pathol 2010 177 2741-2752 DOI 10 2353/ajpath 2010 100377)