Paxillin modulates squamous cancer cell adhesion and is important in pressure-augmented adhesion
Paxillin modulates squamous cancer cell adhesion and is important in pressure-augmented adhesion
复制标题
DOI：
10.1002/jcb.20819
复制
发表时间：
2006-08-15
影响因子：
4
通讯作者：
Basson, Marc D.
中科院分区：
文献类型：
--
作者：
Conway, William C.;van Zyp, Jochem Van der Voort;Basson, Marc D.
帕克西林是一种调节信号转导和局部黏附组装的适配蛋白，在许多恶性肿瘤中都与恶性潜能有关。在侵袭性肿瘤中已发现过表达巴西林。整合素介导局灶性黏附复合体的结合在转移黏附中起重要作用，细胞外压力通过激活FAK和Src上调恶性结肠癌细胞的黏附。在这方面，无论是头颈癌还是帕西林都没有被研究过。我们假设，在基线和细胞外压力增加的情况下，巴西林将在调节鳞癌粘连方面发挥作用。利用稳定转染空选择载体或pAXLIN表达和选择载体的SCC25舌鳞癌细胞，我们研究了在常压或15毫米汞柱加压条件下保持30分钟的细胞对胶原、PXLIN、FAK和Src的粘附性和磷酸化。在环境压力下，过表达巴西林的细胞的粘附率是仅载体细胞(n=6，P<；0.001)的121+/-2.9%。帕西林过表达降低了FAK的磷酸化。压力刺激纯载体细胞黏附到基线的118%+/-12.3%(n=6，P<；0.001)，与其在亲代细胞中的作用相似，并诱导Paxlin、FAK和Src的磷酸化。然而，增加压力并没有刺激帕西林、FAK或Src在帕西林过表达细胞中的黏附或进一步磷酸化。转移性鳞癌细胞的粘附性可通过帕西林的过度表达或在手术过程中细胞外压力或在受限制的隔室内生长而被激活而增加。靶向帕西林的恶性肿瘤患者和手术切除期间的最小肿瘤操作可能是重要的治疗辅助手段。
Paxillin is an adapter protein regulating signaling and focal adhesion assembly that has been linked to malignant potential in many malignancies. Overexpression of paxillin has been noted in aggressive tumors. Integrin-mediated binding through the focal adhesion complex is important in metastatic adhesion and is upregulated by extracellular pressure in malignant colonocytes through FAK and Src activation. Neither head and neck cancers nor paxillin have been studied in this regard. We hypothesized that paxillin would play a role in modulating squamous cancer adhesion both at baseline and under conditions of increased extracellular pressure. Using SCC25 tongue squamous cancer cells stably transfected with either an empty selection vector or paxillin expression and selection vectors, we studied adhesion to collagen, paxillin, FAK, and Src expression and phosphorylation in cells maintained for 30 min under ambient or 15 mmHg increased pressure conditions. Paxillin-overexpressing cells exhibited adhesion 121 +/- 2.9% of that observed in vector-only cells (n = 6, P < 0.001) under ambient pressure. Paxillin-overexpression reduced FAK phosphorylation. Pressure stimulated adhesion to 118 +/- 12.3% (n = 6, P < 0.001) of baseline in vector-only cells, similar to its effect in the parental line, and induced paxillin, FAK, and Src phosphorylation. However, increased pressure did not stimulate adhesion or phosphorylate paxillin, FAK, or Src further in paxillin-overexpressing cells. Metastasizing squamous cancer cell adhesiveness may be increased by paxillin-overexpression or by paxillin activation by extracellular pressure during surgical manipulation or growth within a constraining compartment. Targeting paxillin in patients with malignancy and minimal tumor manipulation during surgical resection may be important therapeutic adjuncts.