CA125/MUC16 interacts with Src family kinases, and over-expression of its C-terminal fragment in human epithelial cancer cells reduces cell-cell adhesion.
MUC16/CA125 is over-expressed in human epithelial tumors including ovarian, breast and some other carcinomas. The purpose of this study is to investigate how cell surface MUC16 is functionally involved in tumor progression, with a special focus on the role of its cytoplasmic tail. Forced expression of C-terminal MUC16 fragment (MUC16C) in epithelial cancer cells increased cell migration. We found that MUC16C directly interacted with Src family kinases (SFKs). Notably, localizations of E-cadherin and β-catenin at the cell-cell contacts were more diffuse in MUC16C transfectants compared with mock transfectants. Furthermore, MUC16C transfectants showed reduced Ca(2+)-dependent cell-cell adhesion, but the treatment of cells with PP2, a SFKs inhibitor, restored this. Because cell surface MUC16 is also associated with the E-cadherin/β-catenin complex, the over-expression of MUC16 and its interaction with SFKs may enhance SFKs-induced deregulation of E-cadherin. Thus, our results suggest a role for cell surface MUC16 in cell-cell adhesion of epithelial cancer cells.
Department of Molecular Biosciences, Faculty of Life Sciences, Kyoto Sangyo University, Kamigamo-Motoyama, Kita-ku, Kyoto 603-8555, Japan. Electronic address: kakita@cc.kyoto-su.ac.jp.
Kaoru
K
Akita
Minami
M
Tanaka
Shuhei
S
Tanida
Yugo
Y
Mori
Munetoyo
M
Toda
Hiroshi
H
Nakada
D018394:CA-125 Antigen / Q000235:genetics / Q000378:metabolism*; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D002448:Cell Adhesion; D002462:Cell Membrane / Q000378:metabolism; D002465:Cell Movement; D003593:Cytoplasm / Q000378:metabolism; D004847:Epithelial Cells / Q000502:physiology*; D045325:HCT116 Cells; D006801:Humans; D061986:MCF-7 Cells; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism; D019061:src-Family Kinases / Q000235:genetics / Q000378:metabolism*
D018394:CA-125 Antigen; D015820:Cadherins; D051176:beta Catenin; D019061:src-Family Kinases
CA125/MUC16; Cell migration; Cell motility; Cell–cell adhesion; Cytoplasmic domain; E-cadherin; Epithelial cancer cells; Membrane-bound mucin; Src family kinases; Tyrosine phosphorylation