RRC ID 52322
Author Yamaguchi H, Ito Y, Miura N, Nagamura Y, Nakabo A, Fukami K, Honda K, Sakai R.
Title Actinin-1 and actinin-4 play essential but distinct roles in invadopodia formation by carcinoma cells.
Journal Eur J Cell Biol
Abstract 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, overexpression 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.
Volume 96(7)
Pages 685-694
Published 2017-10-1
DOI 10.1016/j.ejcb.2017.07.005
PII S0171-9335(17)30061-4
PMID 28797528
MeSH Actinin / genetics* Actins / genetics Breast Neoplasms / genetics* Breast Neoplasms / pathology Cell Line, Tumor Cortactin / genetics Extracellular Matrix / genetics Female Gene Expression Regulation, Neoplastic Gene Knockdown Techniques Humans Neoplasm Invasiveness / genetics Podosomes / genetics* Podosomes / metabolism Time-Lapse Imaging
IF 3.025
Times Cited 8
Human and Animal Cells MDA-MB-453(RCB1192)