Guo Qiusha, Xia Bing, Zhang Feng, Richardson Mekel M, Li Minghao, Zhang Julian S, Chen Feng, Zhang Xin A
Vascular Biology and Cancer Centers and Department of Medicine and Molecular Science, University of Tennessee Health Science Center, Memphis, Tennessee, United States of America.
PLoS One. 2012;7(6):e38464. doi: 10.1371/journal.pone.0038464. Epub 2012 Jun 5.
Alterations in tetraspanin CO-029 expression are associated with the progression and metastasis of cancers in the digestive system. However, how CO-029 promotes cancer metastasis is still poorly understood. To determine the mechanism, we silenced CO-029 expression in HT29 colon cancer cells and found that the CO-029 knockdown significantly reduced cell migratory ability. The diminished cell migration was accompanied by the upregulation of both integrin-dependent cell-matrix adhesion on laminin and calcium-dependent cell-cell adhesion. The cell surface levels of laminin-binding integrin α3β1 and fibronectin-integrin α5β1 were increased while the level of CD44 was decreased upon CO-029 silencing. These changes contribute to the altered cell-matrix adhesion. The deregulated cell-cell adhesion results, at least partially, from increased activity of cadherins and reduced level of MelCAM. In conclusion, CO-029 functions as a regulator of both cell-matrix and cell-cell adhesion. During colon cancer progression, CO-029 promotes cancer cell movement by deregulating cell adhesions.
四跨膜蛋白CO-029表达的改变与消化系统癌症的进展和转移相关。然而，CO-029如何促进癌症转移仍知之甚少。为了确定其机制，我们在HT29结肠癌细胞中沉默了CO-029的表达，发现敲低CO-029显著降低了细胞迁移能力。细胞迁移能力的减弱伴随着层粘连蛋白上整合素依赖性细胞-基质黏附以及钙依赖性细胞-细胞黏附的上调。CO-029沉默后，层粘连蛋白结合整合素α3β1和纤连蛋白-整合素α5β1的细胞表面水平升高，而CD44水平降低。这些变化导致了细胞-基质黏附的改变。细胞-细胞黏附失调至少部分是由于钙黏蛋白活性增加和MelCAM水平降低所致。总之，CO-029作为细胞-基质和细胞-细胞黏附的调节因子发挥作用。在结肠癌进展过程中，CO-029通过失调细胞黏附促进癌细胞移动。
