Filamin B Enhances the Invasiveness of Cancer Cells into 3D Collagen Matrices.
Numerous types of cancer cells migrate into extracellular tissues. This phenomenon is termed invasion, and is associated with poor prognosis in cancer patients. In this study, we demonstrated that filamin B (FLNb), an actin-binding protein, is highly expressed in cancer cell lines that exhibit high invasiveness, with a spindle morphology, into 3D collagen matrices. In addition, we determined that knockdown of FLNb in invasive cancer cells converts cell morphology from spindle-shaped, which is associated with high invasiveness, to round-shaped with low invasiveness. Furthermore, di-phosphorylation of myosin regulatory light chain (MRLC) and phosphorylation of focal adhesion kinase (FAK) are inhibited in FLNb-knockdown cancer cells. These results suggest that FLNb enhances invasion of cancer cells through phosphorylation of MRLC and FAK. Therefore, FLNb may be a new therapeutic target for invasive cancers.
Faculty of Advanced Life Science, Hokkaido University.
Yuta
Y
Iguchi
Seiichiro
S
Ishihara
Yoshimi
Y
Uchida
Kaori
K
Tajima
Takeomi
T
Mizutani
Kazushige
K
Kawabata
Hisashi
H
Haga
D002448:Cell Adhesion; D018929:Cell Culture Techniques; D045744:Cell Line, Tumor; D002465:Cell Movement; D003094:Collagen / Q000737:chemistry; D004847:Epithelial Cells / Q000378:metabolism* / Q000473:pathology; D005347:Fibroblasts / Q000378:metabolism* / Q000473:pathology; D064448:Filamins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D051417:Focal Adhesion Kinase 1 / Q000235:genetics* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D018994:Myosin Light Chains / Q000235:genetics* / Q000378:metabolism; D010766:Phosphorylation; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction
C578662:FLNB protein, human; D064448:Filamins; C466107:MRLC2 protein, human; D018994:Myosin Light Chains; D034741:RNA, Small Interfering; D003094:Collagen; D051417:Focal Adhesion Kinase 1; C496050:PTK2 protein, human