title: Mammary-derived growth inhibitor (MDGI) interacts with integrin α-subunits and suppresses integrin activity and invasion.
abstract: The majority of mortality associated with cancer is due to formation of metastases from the primary tumor. Adhesion mediated by different integrin heterodimers has an important role during cell migration and invasion. Protein interactions with the β1-integrin cytoplasmic tail are known to influence integrin affinity for extracellular ligands, but regulating binding partners for the α-subunit cytoplasmic tails have remained elusive. In this study, we show that mammary-derived growth inhibitor (MDGI) (also known as FABP-3 or H-FABP) binds directly to the cytoplasmic tail of integrin α-subunits and its expression inhibits integrin activity. In breast cancer cell lines, MDGI expression correlates with suppression of the active conformation of integrins. This results in reduced integrin adhesion to type I collagen and fibronectin and inhibition of cell migration and invasion. In tissue microarray of 1331 breast cancer patients, patients with MDGI-positive tumors had more favorable 10-year distant disease-free survival compared with patients with MDGI-negative tumors. Our data indicate that MDGI is a novel interacting partner for integrin α-subunits, and its expression modulates integrin activity and suppresses cell invasion in breast cancer patients. Retained MDGI expression is associated with favorable prognosis.
authors.affiliation: Medical Biotechnology, VTT Technical Research Centre of Finland, Turku, Finland.
authors.forename: J
authors.initials: J
authors.lastname: Nevo
authors.forename: A
authors.initials: A
authors.lastname: Mai
authors.forename: S
authors.initials: S
authors.lastname: Tuomi
authors.forename: T
authors.initials: T
authors.lastname: Pellinen
authors.forename: O T
authors.initials: OT
authors.lastname: Pentikäinen
authors.forename: P
authors.initials: P
authors.lastname: Heikkilä
authors.forename: J
authors.initials: J
authors.lastname: Lundin
authors.forename: H
authors.initials: H
authors.lastname: Joensuu
authors.forename: P
authors.initials: P
authors.lastname: Bono
authors.forename: J
authors.initials: J
authors.lastname: Ivaska
mesh_terms: D000595:Amino Acid Sequence; D001943:Breast Neoplasms / Q000378:metabolism* / Q000401:mortality* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement; D024042:Collagen Type I / Q000378:metabolism; D018572:Disease-Free Survival; D005109:Extracellular Matrix / Q000737:chemistry; D000074026:Fatty Acid Binding Protein 3; D050556:Fatty Acid-Binding Proteins / Q000378:metabolism*; D005260:Female; D005353:Fibronectins / Q000378:metabolism; D006801:Humans; D039001:Integrin alpha Chains / Q000378:metabolism*; D008875:Middle Aged; D008969:Molecular Sequence Data; D009361:Neoplasm Invasiveness; D054730:Protein Interaction Domains and Motifs
chemical_list: D024042:Collagen Type I; C493408:FABP3 protein, human; D000074026:Fatty Acid Binding Protein 3; D050556:Fatty Acid-Binding Proteins; D005353:Fibronectins; D039001:Integrin alpha Chains