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Abrogation of RAB27A expression transiently affects melanoma cell proliferation.
Pigment Cell & Melanoma Research ( IF 4.3 ) Pub Date : 2020-06-08 , DOI: 10.1111/pcmr.12903
Dajiang Guo 1, 2 , Kimberley A Beaumont 1, 2 , Danae M Sharp 1, 2 , Goldie Y L Lui 1, 2 , Wolfgang Weninger 1, 3, 4 , Nikolas K Haass 1, 4, 5 , Shweta Tikoo 1, 2
Affiliation  

The role of the small GTPase RAB27A as an essential melanosome trafficking regulator in melanocytes is well‐accepted. A decade ago, RAB27A was identified as a tumor dependency gene that promotes melanoma cell proliferation. RAB27A has since been linked to another propeller of cancer progression: exosome secretion. We have recently demonstrated that RAB27A is overexpressed in a subset of melanomas. High RAB27A gene and protein expression correlate with poor prognosis in melanoma patients. Mechanistic investigations revealed that the generation of pro‐invasive exosomes was RAB27A‐dependent and, therefore, silencing RAB27A reduced melanoma cell invasion in vitro and in vivo. However, previous studies have implicated RAB27A to be involved in both proliferation and invasion of melanoma cells. Employing four human cell lines, stratified by RAB27A expression, and one RAB27A‐high mouse cell line, we demonstrate in this study that the effects of abrogating RAB27A expression on proliferation are only temporary, in contrast to our previously reported persistent effects on tumor invasion and metastasis. Therefore, we assist in the dissection of the short‐term effects of RAB27A knockdown on melanoma cell proliferation versus long‐term effects on melanoma invasion and metastasis. We believe that our findings provide novel insights into the effects of RAB27A blockade.

中文翻译:

RAB27A 表达的消除会暂时影响黑色素瘤细胞增殖。

小 GTPase RAB27A 作为黑素细胞中必不可少的黑素体运输调节剂的作用已被广泛接受。十年前,RAB27A 被确定为促进黑色素瘤细胞增殖的肿瘤依赖性基因。此后,RAB27A 与癌症进展的另一个推进器有关:外泌体分泌。我们最近证明了 RAB27A 在黑色素瘤的一个子集中过度表达。高 RAB27A 基因和蛋白质表达与黑色素瘤患者的不良预后相关。机制研究表明,促侵袭外泌体的产生是 RAB27A 依赖性的,因此,沉默 RAB27A 可减少体外和体内黑色素瘤细胞的侵袭。然而,之前的研究表明 RAB27A 参与了黑色素瘤细胞的增殖和侵袭。采用四种人类细胞系,通过 RAB27A 表达和一种 RAB27A 高小鼠细胞系分层,我们在本研究中证明,与我们之前报道的对肿瘤侵袭和转移的持续影响相反,废除 RAB27A 表达对增殖的影响只是暂时的。因此,我们协助剖析 RAB27A 敲低对黑色素瘤细胞增殖的短期影响与对黑色素瘤侵袭和转移的长期影响。我们相信我们的发现为 RAB27A 阻断的影响提供了新的见解。我们协助剖析 RAB27A 敲低对黑色素瘤细胞增殖的短期影响与对黑色素瘤侵袭和转移的长期影响。我们相信我们的发现为 RAB27A 阻断的影响提供了新的见解。我们协助剖析 RAB27A 敲低对黑色素瘤细胞增殖的短期影响与对黑色素瘤侵袭和转移的长期影响。我们相信我们的发现为 RAB27A 阻断的影响提供了新的见解。
更新日期:2020-06-08
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