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首页> 外文期刊>Journal of Cellular Physiology >A dominant negative Cx43 mutant differentially affects tumorigenic and invasive properties in human metastatic melanoma cells
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A dominant negative Cx43 mutant differentially affects tumorigenic and invasive properties in human metastatic melanoma cells

机译：主导- Cx43突变不同影响肿瘤发生的和侵略性的属性人类转移性黑色素瘤细胞

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摘要

Previous reports have implicated connexin 43 (Cx43) as a tumor suppressor in early stages of tumorigenesis and in some cases as an enhancer of cell migration in later stages. To address the role of Cx43 in melanoma tumor progression, we utilized two melanoma cell lines derived from the same patient in pre-metastasis (WM793B) and following isolation from a lung metastasis in nude mice (1205Lu). Our results demonstrate a strikingly increased expression of Cx43 in both the pre-metastatic and metastatic melanoma cell lines that were actively migrating compared to non-migrating cells. To further investigate the role of Cx43 in these melanoma cells, we overexpressed wild type (wt) Cx43 as well as a mutant dominant negative Cx43 mutant that causes closed channels (T154A). The metastatic 1205Lu cells expressing Cx43-T154A showed a twofold decrease in colony formation on soft agar while the nonmetastatic WM793B cells showed no significant change. In invasion assays through a collagen matrix, the same Cx43-T154A 1205Lu cells demonstrated a three- to fourfold increase in the invasion index compared to either wt Cx43 or vector control cells. The increase in invasiveness was eliminated by migration towards media with charcoal-stripped serum, suggesting that migration may be directed towards a lipophilic compound(s). Our findings demonstrate that a dominant negative Cx43 mutant deficient in channel formation exhibits a dual pattern of regulation in metastatic melanoma cells with a decrease in anchorage-independent growth and an increase in invasive potential.
机译：之前的报告涉及联接蛋白43(Cx43)作为肿瘤抑制的早期阶段肿瘤发生和在某些情况下的增强剂细胞迁移在以后的阶段。Cx43在黑色素瘤肿瘤恶化,我们利用两个黑素瘤细胞系来源于同一病人pre-metastasis (WM793B)和在隔离的肺转移裸小鼠(1205路)。在这两方面都明显Cx43表达增加pre-metastatic和转移性黑色素瘤细胞积极迁移而行不迁徙的细胞。Cx43的作用在这些黑色素瘤细胞,我们过表达野生型(wt) Cx43以及显性负突变Cx43突变引起关闭通道(T154A)。细胞表达Cx43-T154A表现出双重的在软琼脂集落形成而降低的nonmetastatic WM793B细胞没有明显的变化。胶原蛋白基质,同样Cx43-T154A陆1205细胞增加3到4倍入侵比wt Cx43或指数矢量控制的细胞。侵袭性被迁移对消除媒体与charcoal-stripped血清,建议迁移可能指向亲脂性的化合物(年代)。一个占主导地位的消极Cx43变异缺乏通道形成展览一个双重的模式监管在转移性黑色素瘤细胞减少anchorage-independent增长和一个增加入侵潜力。

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