title: CDCP1 regulates the function of MT1-MMP and invadopodia-mediated invasion of cancer cells.
abstract: Complement C1r/C1s, Uegf, Bmp1 (CUB) domain-containing protein 1 (CDCP1) is a transmembrane protein that regulates anchorage-independent growth and cancer cell migration and invasion. Expression of CDCP1 is detected in a number of cancer cell lines and tissues and is closely correlated with poor prognosis. Invadopodia are actin-based protrusions on the surface of invasive cancer cells that promote the degradation of the extracellular matrix (ECM) via localized proteolysis, which is mainly mediated by membrane type 1 matrix metalloproteinase (MT1-MMP). MT1-MMP is accumulated at invadopodia by targeted delivery via membrane trafficking. The present study shows that CDCP1 is required for ECM degradation by invadopodia in human breast cancer and melanoma cells. CDCP1 localized to caveolin-1-containing vesicular structures and lipid rafts and was detected in close proximity to invadopodia. Further biochemical analysis revealed that substantial amounts of CDCP1 existed in the Triton X-100 insoluble lipid raft fraction. CDCP1 was coimmunoprecipitated with MT1-MMP and colocalized with MT1-MMP at the vesicular structures. The siRNA-mediated knockdown of the CDCP1 expression markedly inhibited MT1-MMP-dependent ECM degradation and Matrigel invasion and reduced the accumulation of MT1-MMP at invadopodia, as shown by immunofluorescence analysis. These results indicate that CDCP1 is an essential regulator of the trafficking and function of MT1-MMP- and invadopodia-mediated invasion of cancer cells.
authors: Division of Metastasis and Invasion Signaling, National Cancer Center Research Institute, Tokyo, Japan.
authors: Yuri
authors: Y
authors: Miyazawa
authors: Takamasa
authors: T
authors: Uekita
authors: Yuumi
authors: Y
authors: Ito
authors: Motoharu
authors: M
authors: Seiki
authors: Hideki
authors: H
authors: Yamaguchi
authors: Ryuichi
authors: R
authors: Sakai
mesh_terms: D015703:Antigens, CD / Q000378:metabolism*; D000951:Antigens, Neoplasm; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology*; D051242:Caveolin 1 / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D045744:Cell Line, Tumor; D022162:Cytoplasmic Vesicles / Q000187:drug effects / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism; D053511:Matrix Metalloproteinase 14 / Q000378:metabolism*; D008545:Melanoma / Q000378:metabolism* / Q000473:pathology*; D021962:Membrane Microdomains / Q000378:metabolism; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000378:metabolism*; D011485:Protein Binding; D021381:Protein Transport; D011554:Pseudopodia / Q000201:enzymology / Q000473:pathology*; D034741:RNA, Small Interfering / Q000378:metabolism
chemical_list: D015703:Antigens, CD; D000951:Antigens, Neoplasm; C432044:CDCP1 protein, human; D051242:Caveolin 1; D015815:Cell Adhesion Molecules; D009363:Neoplasm Proteins; D034741:RNA, Small Interfering; C507086:MMP14 protein, human; D053511:Matrix Metalloproteinase 14