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PMID: 17255943 Published · ppublish English Comparative Study Journal Article Research Support, Non-U.S. Gov't

CIN85, a Cbl-interacting protein, is a component of AMAP1-mediated breast cancer invasion machinery.

The EMBO journal ·Vol. 26 ·No. 3 ·2007-02-07 ·Pages 647-56

Nam JM, Onodera Y, Mazaki Y, Miyoshi H, Hashimoto S, Sabe H

Abstract

Expression of AMAP1 correlates well with the invasive phenotypes and malignancy of human primary breast carcinomas. AMAP1 recruits its binding proteins, such as cortactin and paxillin, to sites of Arf6 activation to form invadopodia. A mouse ortholog of AMAP1, ASAP1, is known to bind to CIN85, a binding partner of an E3 ligase, Cbl. Here, we found that CIN85 colocalizes with AMAP1 at invadopodia, and binding of AMAP1 with CIN85 is important for the invasive activities of breast cancer cells, including MDA-MB-231. siRNA-mediated silencing of CIN85, as well as Cbl, also inhibited the invasion. We moreover found that AMAP1 is monoubiquitinated, rather than polyubiquitinated, by virtue of Cbl and provide evidence that the ability of AMAP1 to be monoubiquitinated is important for its involvement in invasion. Our results indicate that CIN85, as well as Cbl, which is a well-known suppressor of growth factor receptor signaling, can be positively involved in tumor invasion, and suggest that a complex epigenetic process is involved in AMAP1 function in breast cancer cell invasion.

MeSH Terms
Adaptor Proteins, Signal Transducing/metabolism Breast Neoplasms/metabolism,physiopathology Carrier Proteins/metabolism Cell Line, Tumor Cell Surface Extensions/metabolism Female Humans Immunoblotting Immunoprecipitation Neoplasm Invasiveness/physiopathology Protein Binding Ubiquitin/metabolism
Chemicals
Adaptor Proteins, Signal Transducing Carrier Proteins MYCBPAP protein, human SH3KBP1 protein, human Ubiquitin
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Nam Jin-Min
Department of Molecular Biology, Osaka Bioscience Institute, Suita, Osaka, Japan.
Onodera Yasuhito
Mazaki Yuichi
Miyoshi Hiroyuki
Hashimoto Shigeru
Sabe Hisataka
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
DOI
10.1038/sj.emboj.7601534
Published
2007-02-07
Epub
2007-00-25
Pages
647-56
Language
English
Region
England
NLM ID
8208664
PMCID
PMC1794391
Subset
IM
External Links
PubMed source DOI: 10.1038/sj.emboj.7601534 PMC Full Text View journal details
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