Expression of the focal adhesion protein paxillin in lung cancer and its relation to cell motility
Expression of the focal adhesion protein paxillin in lung cancer and its relation to cell motility
复制标题
DOI：
10.1038/sj.onc.1202273
复制
发表时间：
1999-01-07
期刊：
影响因子：
8
通讯作者：
Sugarbaker, DJ
中科院分区：
文献类型：
--
作者：
Salgia, R;Li, JL;Sugarbaker, DJ
肺癌可导致肌动蛋白细胞骨架结构的异常，这在转化中可能是重要的。在这项研究中，我们研究了细胞骨架相关蛋白桩蛋白在肺癌中的表达，桩蛋白是一种68 kDa的粘着斑蛋白，在C端具有四个串联的LIM结构域，参与生长因子受体，整合素和致癌信号，如v-src，BCR/ABL和乳头状瘤病毒的E6。在非小细胞肺癌（NSCLC）细胞系中，桩蛋白定位于粘着斑。通过在两个单独的NSCLC细胞系（Calu-1和H661）中过表达绿色荧光蛋白（GFP）-桩蛋白构建体来评估桩蛋白在肺癌细胞中的可能作用。在48小时的过程中，与正常对照、GFP-N-末端桩蛋白或GFP-LIM转染的细胞相比，GFP-桩蛋白一致地引起细胞变圆并降低细胞运动性。由于某些肺癌可能具有相当高的侵袭性和快速转移性，这可能与细胞骨架有关，因此我们测定了桩蛋白在NSCLC和小细胞肺癌（SCLC）细胞系和患者肿瘤组织中的表达。采用北方印迹和Western印迹分析paxillin在NSCLC和SCLC细胞系中的表达。桩蛋白在小细胞肺癌细胞系中的表达一直较低，而在非小细胞肺癌细胞系中有桩蛋白表达。与正常肺组织相比，桩蛋白在NSCLC肿瘤组织中的表达存在变异性。相反，通过免疫组化，我们发现在5/5例SCLC患者中没有可检测到的桩蛋白表达。这些数据表明，桩蛋白表达的缺乏或低水平可能导致某些肺癌，如SCLC，更具运动性和可能更具侵略性。
Lung cancer can lead to abnormalities of the actin cytoskeleton structure which may be important in transformation. In this study, we have investigated the expression of the cytoskeletal associated protein paxillin in lung cancer, Paxillin is a 68 kDa focal adhesion protein, with four tandem LIM domains at the C-terminus, involved in growth factor receptor, integrin and oncogenic signaling such as v-src, BCR/ABL, and E6 of the papilloma virus. In non-small cell lung cancer (NSCLC) cell lines, paxillin localized to the focal adhesions. The possible role of paxillin in lung cancer cells was assessed by overexpressing green fluorescence protein (GFP)-paxillin construct in two separate NSCLC cell lines (Calu-1 and H661), Over the course of 48 h, GFP-paxillin consistently caused the cells to become round and to decrease cell motility as compared to normal controls, GFP-N-terminus paxillin, or GFP-LIM transfected cells. Because some lung cancers may be quite aggressive and metastasize quickly, which may be related to the cytoskeleton, we determined the expression of paxillin in NSCLC and small cell lung cancer (SCLC) cell lines and patient tumor tissues. Expression of paxillin in NSCLC and SCLC cell lines were determined by Northern blot and Western blot analysis. The expression of paxillin was consistently low in SCLC cell lines, whereas there was paxillin expression in NSCLC cell lines. There was a variability of expression of paxillin in NSCLC tumor tissue as compared to normal lung tissue. In contrast, by immunohistochemistry, we show that there was no detectable expression of paxillin in 5/5 SCLC patients. This data suggests that absence or low level of paxillin protein expression may cause certain lung cancers, such as SCLC, to be more motile and possibly more aggressive.