Document Detail

p120-catenin is required for the collective invasion of squamous cell carcinoma cells via a phosphorylation-independent mechanism.
MedLine Citation:
PMID:  17334396     Owner:  NLM     Status:  MEDLINE    
Loss of E-cadherin-mediated cell-cell junctions has been correlated with cancer cell invasion and poor patient survival. p120-catenin has emerged as a key player in promoting E-cadherin stability and adherens junction integrity and has been proposed as a potential invasion suppressor by preventing release of cells from the constraints imposed by cadherin-mediated cell-cell adhesion. However, it has been proposed that tyrosine phosphorylation of p120 may contribute to cadherin-dependent junction disassembly during invasion. Here, we use small interfering RNA (siRNA) in A431 cells to show that knockdown of p120 promotes two-dimensional migration of cells. In contrast, p120 knockdown impairs epidermal growth factor-induced A431 invasion into three-dimensional matrix gels or in organotypic culture, whereas re-expression of siRNA-resistant p120, or a p120 isoform that cannot be phosphorylated on tyrosine, restores the collective mode of invasion employed by A431 cells in vitro. Thus, p120 promotes A431 cell invasion in a phosphorylation-independent manner. We show that the collective invasion of A431 cells depends on the presence of cadherin-mediated (P- and E-cadherin) cell-cell contacts, which are lost in cells where p120 expression is knocked down. Furthermore, membranous p120 is maintained in invasive squamous cell carcinomas in tumours suggesting that p120 may be important for the collective invasion of tumours cells in vivo.
I R Macpherson; S Hooper; A Serrels; L McGarry; B W Ozanne; K Harrington; M C Frame; E Sahai; V G Brunton
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Publication Detail:
Type:  Journal Article     Date:  2007-03-05
Journal Detail:
Title:  Oncogene     Volume:  26     ISSN:  0950-9232     ISO Abbreviation:  Oncogene     Publication Date:  2007 Aug 
Date Detail:
Created Date:  2007-08-09     Completed Date:  2007-10-12     Revised Date:  2010-01-29    
Medline Journal Info:
Nlm Unique ID:  8711562     Medline TA:  Oncogene     Country:  England    
Other Details:
Languages:  eng     Pagination:  5214-28     Citation Subset:  IM    
The Beatson Institute for Cancer Research, Glasgow, UK.
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MeSH Terms
Base Sequence
Carcinoma, Squamous Cell / pathology*
Cell Adhesion Molecules / chemistry,  metabolism,  physiology*
Cell Line, Tumor
DNA Primers
Epidermal Growth Factor / metabolism
Neoplasm Invasiveness*
Phosphoproteins / chemistry,  metabolism,  physiology*
RNA, Small Interfering
Recombinant Proteins / metabolism
Tyrosine / metabolism
Reg. No./Substance:
0/Cell Adhesion Molecules; 0/DNA Primers; 0/Phosphoproteins; 0/RNA, Small Interfering; 0/Recombinant Proteins; 0/delta catenin; 55520-40-6/Tyrosine; 62229-50-9/Epidermal Growth Factor

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