Role of EIF5A2, a downstream target of Akt, in promoting melanoma cell invasion.
Role of EIF5A2, a downstream target of Akt, in promoting melanoma cell invasion.
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DOI：
10.1038/bjc.2013.688
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发表时间：
2014-01-21
影响因子：
8.8
通讯作者：
Li, G.
中科院分区：
文献类型：
--
作者：
Khosravi, S.;Wong, R. P. C.;Ardekani, G. S.;Zhang, G.;Martinka, M.;Ong, C. J.;Li, G.
皮肤黑色素瘤是一种威胁生命的皮肤癌，因为它的侵袭性和高转移潜力鲜为人知。本研究探讨了真核细胞翻译起始因子5A2(EIF5A2)在黑色素瘤发病机制中的重要性。我们用组织芯片检测了459例黑素细胞皮损中EIF5A2的表达。此外，对黑色素瘤细胞株进行了侵袭和细胞增殖分析、酶谱分析、流式细胞仪和实时荧光定量聚合酶链式反应，以探讨EIF5A2在肿瘤进展中的作用。EIF5A2阳性表达从发育不良痣到原发黑色素瘤逐渐增强(P=0.001)，在转移性黑色素瘤中进一步增强(P=0.044)。真核细胞翻译起始因子5A2的表达与黑色素瘤厚度相关(P<；0.001)，与PM患者，尤其是⩽2 mm厚的患者的5年生存期呈负相关。值得注意的是，EIF5A2阴性组无一例在5年内死亡。COX回归分析显示，EIF5A2是一个独立的预后指标。进一步，我们发现EIF5A2是一个新的磷酸化Akt的下游靶点。EIF5A2过表达和EIF5A2基因敲除后，黑色素瘤细胞侵袭力增加，MMP2活性降低。我们首次发现EIF5A2作为PI3K/Akt的靶点，能够促进黑色素瘤细胞的侵袭，有望成为黑色素瘤的预后标志物和潜在的治疗靶点。
Cutaneous melanoma is a life-threatening skin cancer because of its poorly understood invasive nature and high metastatic potential. This study examines the importance of eukaryotic translation initiation factor 5A2 (EIF5A2) in melanoma pathogenesis. We examined EIF5A2 expression in 459 melanocytic lesions using tissue microarray. In addition, melanoma cell lines were subjected to invasion and cell proliferation assays, zymography, FACS and real-time PCR to investigate the role of EIF5A2 in cancer progression. Positive EIF5A2 staining increased from dysplastic naevi to primary melanomas (PMs; P=0.001), and further increased in metastatic melanomas (P=0.044). Eukaryotic translation initiation factor 5A2 expression was correlated with melanoma thickness (P<0.001) and was inversely correlated with the 5-year survival of PM patients especially those with tumour⩽2 mm thick. Strikingly, none of the latter died within 5 years in EIF5A2-negative staining group. Cox regression analysis revealed that EIF5A2 is an independent prognostic marker. Further, we found that EIF5A2 is a novel downstream target of phosphorylated Akt. Both melanoma cell invasion and MMP-2 activity increased and decreased with EIF5A2 overexpression and knockdown, respectively. We for the first time showed that EIF5A2, as a target of PI3K/Akt, promotes melanoma cell invasion and may serve as a promising prognostic marker and a potential therapeutic target for melanoma.
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影响因子：
11.2
作者：
Chow HY;Jubb AM;Koch JN;Jaffer ZM;Stepanova D;Campbell DA;Duron SG;O'Farrell M;Cai KQ;Klein-Szanto AJ;Gutkind JS;Hoeflich KP;Chernoff J
通讯作者：
Chernoff J
DOI：
10.1046/j.1432-1033.2003.03806.x
发表时间：
2003-11-01
期刊：
EUROPEAN JOURNAL OF BIOCHEMISTRY
影响因子：
--
作者：
Clement, PMJ;Henderson, CA;Johansson, HE
通讯作者：
Johansson, HE
DOI：
10.1073/pnas.060579697
发表时间：
2000-03-28
影响因子：
11.1
作者：
Persad, S;Attwell, S;Dedhar, S
通讯作者：
Dedhar, S
影响因子：
45.3
作者：
Karjalainen, JM;Kellokoski, JK;Kosma, VM
通讯作者：
Kosma, VM
影响因子：
64.8
作者：
SATO, H;TAKINO, T;SEIKI, M
通讯作者：
SEIKI, M