title: CIN85, a Cbl-interacting protein, is a component of AMAP1-mediated breast cancer invasion machinery.
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.
authors.affiliation: Department of Molecular Biology, Osaka Bioscience Institute, Suita, Osaka, Japan.
authors.forename: Jin-Min
authors.initials: JM
authors.lastname: Nam
authors.forename: Yasuhito
authors.initials: Y
authors.lastname: Onodera
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Mazaki
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Miyoshi
authors.forename: Shigeru
authors.initials: S
authors.lastname: Hashimoto
authors.forename: Hisataka
authors.initials: H
authors.lastname: Sabe
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D001943:Breast Neoplasms / Q000378:metabolism / Q000503:physiopathology*; D002352:Carrier Proteins / Q000378:metabolism*; D045744:Cell Line, Tumor; D022081:Cell Surface Extensions / Q000378:metabolism*; D005260:Female; D006801:Humans; D015151:Immunoblotting; D047468:Immunoprecipitation; D009361:Neoplasm Invasiveness / Q000503:physiopathology*; D011485:Protein Binding; D025801:Ubiquitin / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; C465633:MYCBPAP protein, human; C433810:SH3KBP1 protein, human; D025801:Ubiquitin