期刊
EUROPEAN JOURNAL OF CELL BIOLOGY
卷 96, 期 7, 页码 685-694出版社
ELSEVIER GMBH, URBAN & FISCHER VERLAG
DOI: 10.1016/j.ejcb.2017.07.005
关键词
Invadopodia; Actinin-1; Actinin-4; Cancer invasion; Extracellular matrix
类别
资金
- JSPS KAKENHI [JP25430126, JP16K14622]
- Kanzawa Medical Research Foundation
- Kanae Foundation for the Promotion of Medical Science
- Sumitomo Foundation
- Takeda Science Foundation
- Grants-in-Aid for Scientific Research [16K14622, 17H04051, 16K14616, 26290043] Funding Source: KAKEN
Invadopodia are ventral membrane protrusions formed by cancer cells that degrade the extracellular matrix (ECM) during tumor invasion and metastasis. Formation of invadopodia is initiated by the assembly of actin filaments (F-actin) that results from the coordinated activation of several actin regulatory proteins. Actinin-1 and actinin-4 are actin bundling proteins expressed in non-muscle cells and actinin-4 is preferentially associated with malignant phenotypes of carcinoma cells. In this study, we investigated the role of actinin-1 and -4 in invadopodia formation. Expression of both actinin-1 and -4 tended to be higher in invasive and metastatic breast carcinoma cell lines than in non-invasive ones. Immunofluorescence analysis revealed that actinin-1 and -4 colocalized at core actin structures of invadopodia. Time-lapse imaging showed that appearance of both actinins at invadopodia is concomitant with the assembly of F-actin. Knockdown of either actinin-1 or actinin-4 suppressed the formation of invadopodia and degradation of the ECM by carcinoma cells. Interestingly, over expression of actinin-4, but not actinin-1, significantly promoted the formation of invadopodia and this activity required the actin binding domains and the unique N-terminal motif that exists only in actinin-4. These results demonstrate that both actinin-1 and actinin-4 participate in the assembly of F-actin at invadopodia. Additionally, actinin-4 may have a selective advantage in accelerating invadopodia-mediated invasion of carcinoma cells.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据