Rodrigue Christelle M, Porteu Françoise, Navarro Nicole, Bruyneel Erik, Bracke Marc, Romeo Paul-Henri, Gespach Christian, Garel Marie-Claude
INSERM U567, UMR 8104, Département d'Hématologie, Institut Cochin, Université Paris V, Maternité Port-Royal, 123 boulevard de Port-Royal, Paris 75014, France.
Oncogene. 2005 May 5;24(20):3274-84. doi: 10.1038/sj.onc.1208485.
During a search to identify resveratrol (3,5,4'-trihydroxy-trans-stilbene, RV) target genes in the human erythroleukemic K562 cell line, we show here that the tensin gene and protein levels are remarkably induced by this dietary polyphenol. Tensin, a cell-matrix adhesion protein binding the integrins and cytoskeletal actin filaments also interacts with PI3-kinase and JNK signaling pathways. Tensin induction by RV is associated with increased K562 cell adhesion to fibronectin, cell spreading and actin polymerization. The same responses were observed in the tensin-deficient MCF7 human breast cancer cell line. In K562 and MCF7 cells treated by RV, tensin was found in punctate and intracytoplasmic areas. In MCF7 epithelial cells, induction of tensin is not exclusively associated with plasma membrane-bound vinculin, suggesting a dual localization of tensin in both focal and fibrillar adhesions. Pharmacological blockade of PI3-kinase and Rho GTPases/Rho-kinase resulted in selective depletion of focal adhesions, disorganization of tensin localization and disruption of stress fibers. RV increased cell motility and attachment to fibronectin in MCF7 cells submitted to mechanical laminar flow stress, and abrogated estrogen-induced MCF7 cancer cell invasion. Our data support the conclusion that induction of tensin by RV contributes to the chemopreventive and anti-invasive activity of this natural dietary compound in tensin-negative and -deficient leukemic cells or epithelioid cancers.
在寻找人类红白血病K562细胞系中白藜芦醇（3,5,4'-三羟基反式芪，RV）的靶基因的过程中，我们在此表明，这种膳食多酚可显著诱导张力蛋白的基因和蛋白水平。张力蛋白是一种结合整合素和细胞骨架肌动蛋白丝的细胞 - 基质粘附蛋白，它还与PI3激酶和JNK信号通路相互作用。RV诱导张力蛋白与K562细胞对纤连蛋白的粘附增加、细胞铺展和肌动蛋白聚合有关。在缺乏张力蛋白的MCF7人乳腺癌细胞系中也观察到了相同的反应。在用RV处理的K562和MCF7细胞中，张力蛋白出现在点状和胞质内区域。在MCF7上皮细胞中，张力蛋白的诱导并不完全与质膜结合的纽蛋白相关，这表明张力蛋白在粘着斑和纤维状粘着斑中都有双重定位。PI3激酶和Rho GTP酶/Rho激酶的药理学阻断导致粘着斑选择性耗竭、张力蛋白定位紊乱和应力纤维破坏。在受到机械层流应力的MCF7细胞中，RV增加了细胞运动性和对纤连蛋白的附着，并消除了雌激素诱导的MCF7癌细胞侵袭。我们的数据支持这样的结论：RV诱导张力蛋白有助于这种天然膳食化合物在张力蛋白阴性和缺乏的白血病细胞或上皮样癌中的化学预防和抗侵袭活性。
