Podocalyxin-like protein, linked to poor prognosis of pancreatic cancers, promotes cell invasion by binding to gelsolin.
Podocalyxin-like protein, linked to poor prognosis of pancreatic cancers, promotes cell invasion by binding to gelsolin.
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DOI：
10.1111/cas.13018
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发表时间：
2016-10
期刊：
影响因子：
5.7
通讯作者：
Saibara T
中科院分区：
文献类型：
--
作者：
Taniuchi K;Furihata M;Naganuma S;Dabanaka K;Hanazaki K;Saibara T
细胞粘附糖蛋白PODXL与几种癌症形式中的侵袭性肿瘤表型相关。在这里，我们报告说，高PODXL表达是胰腺癌患者总生存率较差的独立预测因子，PODXL通过与细胞骨架蛋白凝溶胶蛋白的物理结合促进胰腺癌细胞的运动和侵袭。抑制PODXL或凝溶胶蛋白减少膜突起与丰富的周边肌动蛋白结构，并反过来抑制细胞的运动和侵袭。转染PODXL拯救构建体更新了与细胞突起中的外周肌动蛋白结构结合的凝溶胶蛋白的表达，并消除了由PODXL敲低引起的细胞突起减少。此外，将PODXL拯救构建体转染到其中PODXL和凝溶胶蛋白均被抑制的胰腺癌细胞中未能增加突起的形成。因此，PODXL通过增加细胞突起中的凝溶胶蛋白-肌动蛋白相互作用来增强运动性和侵袭性。
The cell‐adhesion glycoprotein PODXL is associated with an aggressive tumor phenotype in several forms of cancer. Here, we report that high PODXL expression was an independent predictor of worse overall survival of pancreatic cancer patients, and that PODXL promoted pancreatic cancer cell motility and invasion by physically binding to the cytoskeletal protein gelsolin. Suppression of PODXL or gelsolin decreased membrane protrusions with abundant peripheral actin structures, and in turn inhibited cell motility and invasion. Transfection of a PODXL‐rescue construct renewed the expression of gelsolin bound to peripheral actin structures in cell protrusions, and abrogated the decreased cell protrusions caused by the knockdown of PODXL. Furthermore, transfection of a PODXL‐rescue construct into pancreatic cancer cells in which both PODXL and gelsolin were suppressed failed to increase the formation of the protrusions. Thus, PODXL enhances motility and invasiveness through an increase in gelsolin–actin interactions in cell protrusions.
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影响因子：
3.7
作者：
Nielsen JS;Graves ML;Chelliah S;Vogl AW;Roskelley CD;McNagny KM
通讯作者：
McNagny KM
影响因子：
6
作者：
Hsu, Yung-Ho;Lin, Wei-Ling;Jou, Tzuu-Shuh
通讯作者：
Jou, Tzuu-Shuh
影响因子：
5
作者：
Lee, KM;Yasuda, H;Ouellette, MM
通讯作者：
Ouellette, MM
影响因子：
11.4
作者：
De Corte, V;Bruyneel, E;Gettemans, J
通讯作者：
Gettemans, J
影响因子：
64.8
作者：
JANMEY, PA;STOSSEL, TP
通讯作者：
STOSSEL, TP