Connexin 43 expression is associated with increased malignancy in prostate cancer cell lines and functions to promote migration.
Connexin 43 expression is associated with increased malignancy in prostate cancer cell lines and functions to promote migration.
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DOI：
10.18632/oncotarget.3449
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发表时间：
2015-05-10
期刊：
影响因子：
--
通讯作者：
Lathia JD
中科院分区：
文献类型：
--
作者：
Zhang A;Hitomi M;Bar-Shain N;Dalimov Z;Ellis L;Velpula KK;Fraizer GC;Gourdie RG;Lathia JD
连接蛋白（促进细胞间直接通讯的差距连接亚基）表达受损与前列腺癌生长有关。为了阐明连接蛋白在前列腺癌进展中的关键作用，我们对恶性肿瘤谱中四种代表性前列腺癌细胞系中连接蛋白的表达进行了系统的定量RT-PCR筛选。在所有四个细胞系中检测到几个连接蛋白亚基的转录本，并且连接蛋白43（Cx43）在具有增加的转移潜能的细胞中在RNA和蛋白水平上显示出显著的升高。间隙连接介导的细胞间通讯的分析显示，在PC-3细胞，其中有最高的Cx43的表达，与最小的耦合在LNCaP细胞，其中Cx43的表达是非常低的同源偶联。用差距连接抑制剂甘珀酸或连接蛋白模拟肽ACT-1处理没有损害细胞生长，表明生长独立于功能性间隙连接。与表达非靶向shRNA的对照细胞相比，通过shRNA降低Cx43表达的PC-3细胞在单层伤口愈合试验中显示出降低的迁移，以及降低的transwell侵袭能力。这些结果以及Cx43表达水平与细胞系转移能力之间的相关性表明Cx43在前列腺癌侵袭和转移中的作用。
Impaired expression of connexins, the gap junction subunits that facilitate direct cell-cell communication, have been implicated in prostate cancer growth. To elucidate the crucial role of connexins in prostate cancer progression, we performed a systematic quantitative RT-PCR screening of connexin expression in four representative prostate cancer cell lines across the spectrum of malignancy. Transcripts of several connexin subunits were detected in all four cell lines, and connexin 43 (Cx43) showed marked elevation at both RNA and protein levels in cells with increased metastatic potential. Analysis of gap-junction-mediated intercellular communication revealed homocellular coupling in PC-3 cells, which had the highest Cx43 expression, with minimal coupling in LNCaP cells where Cx43 expression was very low. Treatment with the gap junction inhibitor carbenoxolone or connexin mimetic peptide ACT-1 did not impair cell growth, suggesting that growth is independent of functional gap junctions. PC-3 cells with Cx43 expression reduced by shRNA showed decreased migration in monolayer wound healing assay, as well as decreased transwell invasion capacities when compared to control cells expressing non-targeting shRNA. These results, together with the correlation between Cx43 expression levels and the metastatic capacity of the cell lines, suggest a role of Cx43 in prostate cancer invasion and metastasis.
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影响因子：
11.2
作者：
McLachlan, Elizabeth;Shao, Qing;Laird, Dale W.
通讯作者：
Laird, Dale W.
影响因子：
4
作者：
Lamiche, Coralie;Clarhaut, Jonathan;Cronier, Laurent
通讯作者：
Cronier, Laurent
影响因子：
23.9
作者：
Lathia JD;Gallagher J;Heddleston JM;Wang J;Eyler CE;Macswords J;Wu Q;Vasanji A;McLendon RE;Hjelmeland AB;Rich JN
通讯作者：
Rich JN
影响因子：
4.8
作者：
MEDA, P;PEPPER, MS;ORCI, L
通讯作者：
ORCI, L
影响因子：
1.2
作者：
Justus, Calvin R.;Leffler, Nancy;Yang, Li V.
通讯作者：
Yang, Li V.