AFAP-110 is required for actin stress fiber formation and cell adhesion in MDA-MB-231 breast cancer cells
AFAP-110 is required for actin stress fiber formation and cell adhesion in MDA-MB-231 breast cancer cells
复制标题
DOI：
10.1002/jcp.21143
复制
发表时间：
2007-12-01
影响因子：
5.6
通讯作者：
Flynn, Daniel C.
中科院分区：
文献类型：
--
作者：
Dorfleutner, Andrea;Stehlik, Christian;Flynn, Daniel C.
肌动蛋白组织和动力学的调节是一个高度复杂的过程，涉及许多肌动蛋白结合蛋白，包括加帽，分支，切断，螯合和交联蛋白。肌动蛋白结合和交联蛋白AFAP-110在正常肌上皮细胞中表达。不同乳腺上皮细胞系的筛选揭示了AFAP-110在人乳腺癌细胞系MDA-MB-231和MDA-MB-435中的高表达水平。MDA-MB-231细胞中AFAP-110表达的敲低不导致细胞增殖的任何变化，但确实导致肌动蛋白应力纤维交联的损失和与纤连蛋白的粘附降低。一种可诱导的敲低方法证实，MDA-MB-231乳腺癌细胞需要AFAP-110表达以形成应力纤维和粘附。因此，AFAP-110可以通过应力纤维形成提供细胞骨架张力，这是粘着斑形成所需的。事实上，在AFAP-110敲除细胞粘附到纤连蛋白后，我们不能检测到任何局灶性接触或局灶性粘附。虽然关键的粘着斑成分的表达水平不受AFAP-110表达水平的影响，但用LPA处理AFAP-110敲低细胞并不导致肌动蛋白应力纤维和粘着斑的诱导。总之，AFAP-110在MDA-MB-231乳腺癌细胞粘附中起重要作用，可能通过调节应力丝交联而促进粘着斑形成。
Regulation of actin organization and dynamics is a highly complex process that involves a number of actin-binding proteins, including capping, branching, severing, sequestering, and cross-linking proteins. The actin-binding and cross-linking protein AFAP-110 is expressed in normal myoepithelial cells. Screening of different breast epithelial cell lines revealed high expression levels of AFAP-110 in the human breast cancer cell lines MDA-MB-231 and MDA-MB-435. Knockdown of AFAP-110 expression in MDA-MB-231 cells does not result in any changes in cell proliferation but did result in a loss of actin stress fiber cross-linking and decreased adhesion to fibronectin. An inducible knockdown approach confirms that MDA-MB-231 breast cancer cells require AFAP-110 expression for stress fiber formation and adhesion. Thus, AFAP-110 may provide cytoskeletal tension through stress fiber formation, which is required for focal adhesion formation. Indeed, we could not detect any focal contacts or focal adhesions in AFAP-110 knockdown cells after adhesion to fibronectin. Although expression levels of crucial focal adhesion components were not influenced by AFAP-110 expression levels, treatment of AFAP-110 knockdown cells with LPA did not result in induction of actin stress fibers and focal adhesions. In summary, AFAP-110 plays an important role in MDA-MB-231 breast cancer cell adhesion possibly by regulating stress filament cross-linking which would promote focal adhesion formation.