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RESEARCH PRODUCT
Mammary-derived growth inhibitor (MDGI) interacts with integrin α-subunits and suppresses integrin activity and invasion
Heikki JoensuuPetri BonoSaara TuomiSaara TuomiJohan LundinAnja MaiAnja MaiOlli T. PentikäinenTeijo PellinenTeijo PellinenJonna NevoPäivi HeikkiläJohanna IvaskaJohanna IvaskaJohanna Ivaskasubject
Cancer Researchmedicine.disease_causemigrationCD49cCollagen receptor0302 clinical medicineCell Movement0303 health sciencesCell migrationMiddle Agedinvasion3. Good healthCell biologyExtracellular MatrixadhesionIntegrin alpha MMDGI030220 oncology & carcinogenesis/dk/atira/pure/sustainabledevelopmentgoals/good_health_and_well_beingIntegrin beta 6FemaleFatty Acid Binding Protein 3Integrin alpha Chainsmedicine.medical_specialtyintegrinIntegrinMolecular Sequence DataBreast NeoplasmsBiologyFatty Acid-Binding ProteinsCollagen Type IDisease-Free Survival03 medical and health sciencesbreast cancerSDG 3 - Good Health and Well-beingInternal medicineCell Line TumorGeneticsmedicineHumansNeoplasm InvasivenessProtein Interaction Domains and MotifsAmino Acid SequenceMolecular Biology030304 developmental biologyFibronectinsFibronectinEndocrinologybiology.proteinCarcinogenesisdescription
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.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2010-01-01 | Oncogene |