Maspin is physically associated with [beta]1 integrin regulating cell adhesion in mammary epithelial cells.
Maspin is a tumor-suppressor serpin (serine protease inhibitor), which inhibits cell invasion and migration. Here, we analyzed maspin function in cell adhesion in nontransformed mammary epithelial cells and investigated the underlying mechanism involved in this process. We report that maspin acts in the early steps in the cell adhesion process. Addition of recombinant maspin rapidly increased MCF-10A cell adhesion to the endogenously deposited matrix, and conversely both an antimaspin antibody (Ab) and maspin knockdown by RNA interference resulted in decreased cell adhesion. Mutation analyses revealed that a region of 86 amino acids located between aa 139 and aa 225 was responsible for maspin effect on adhesion. In addition, we show that maspin is associated with detergent-insoluble cortical cytoskeleton elements. Collectively, these results suggest that maspin is part of the supramolecular structure of the adhesion plaque and it modulates cell adhesion via a beta1 integrin-dependent mechanism.
Cella
Nathalie
N
Baylor College of Medicine, Department of Molecular and Cellular Biology, ALKEK Bldg., Rm. N630, One Baylor Plaza, Houston, Texas 77030, USA.
Contreras
Alejandro
A
Latha
Khatri
K
Rosen
Jeffrey M
JM
Zhang
Ming
M
D001483:Base Sequence; D001940:Breast / Q000502:physiology*; D001943:Breast Neoplasms; D002448:Cell Adhesion / Q000502:physiology*; D045744:Cell Line, Tumor; D017931:DNA Primers; D004847:Epithelial Cells / Q000502:physiology; D016147:Genes, Tumor Suppressor / Q000502:physiology*; D006801:Humans; D019012:Integrin beta1 / Q000502:physiology; D034622:RNA Interference; D011994:Recombinant Proteins / Q000378:metabolism; D015842:Serine Proteinase Inhibitors; D015843:Serpins / Q000235:genetics / Q000502:physiology*
D017931:DNA Primers; D019012:Integrin beta1; D011994:Recombinant Proteins; C085344:SERPIN-B5; D015842:Serine Proteinase Inhibitors; D015843:Serpins