Daniel-Wójcik Anna, Misztal Katarzyna, Bechyne Iga, Sroka Jolanta, Miekus Katarzyna, Madeja Zbigniew, Czyz Jaroslaw
Department of Cell Biology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, 30-387 Kraków, Poland.
Int J Oncol. 2008 Aug;33(2):309-15.
Connexins and gap junctions play a crucial role during carcinogenesis. While diverse regulatory systems have been shown to modulate their function, the influence of cell motility on the intensity of gap junctional intercellular coupling has yet to be systematically addressed. Since cancer cell motility and intercellular coupling determine cancer development, we aimed at elucidating how mutual cell translocation modulates the intensity of gap junctional coupling in cell populations. Time-lapse analyses of the motility of connexin43 (Cx43)-coupled rat prostate carcinoma (MAT-LyLu) and mouse melanoma (B16) cells cultured on hyper-adhesive substrata revealed a reduced intensity of intercellular translocations in the two cell populations compared to the control conditions. While no detectable effects on the architecture of the actin cytoskeleton and Cx43 expression and phosphorylation were observed, the inhibition of cell motility was paralleled by an increase in the abundance of Cx43-positive plaques in cell-to-cell contacts and an enhancement of gap junctional coupling in cell populations cultured on hyper-adhesive substrata. Thus, a direct correlation between two cellular parameters crucial for carcinogenesis, i.e. cell motility and gap junctional coupling intensity exists in cancer cell populations.
连接蛋白和间隙连接在致癌过程中起着至关重要的作用。虽然多种调节系统已被证明可调节它们的功能，但细胞运动性对间隙连接细胞间偶联强度的影响尚未得到系统研究。由于癌细胞的运动性和细胞间偶联决定了癌症的发展，我们旨在阐明细胞间的相互移位如何调节细胞群体中间隙连接偶联的强度。对在高黏附性基质上培养的、由连接蛋白43（Cx43）介导偶联的大鼠前列腺癌（MAT-LyLu）细胞和小鼠黑色素瘤（B16）细胞的运动性进行延时分析发现，与对照条件相比，这两种细胞群体中的细胞间移位强度降低。虽然未观察到对肌动蛋白细胞骨架的结构以及Cx43的表达和磷酸化有可检测到的影响，但在高黏附性基质上培养的细胞群体中，细胞运动性的抑制伴随着细胞间接触中Cx43阳性斑块丰度的增加以及间隙连接偶联的增强。因此，在癌细胞群体中，致癌过程中两个关键的细胞参数，即细胞运动性和间隙连接偶联强度之间存在直接关联。
