Mammary-derived growth inhibitor (MDGI) interacts with integrin α-subunits and suppresses integrin activity and invasion

• Published in: Oncogene Vol. 29; no. 49; pp. 6452 - 6463
• Main Authors: Nevo, J, Mai, A, Tuomi, S, Pellinen, T, Pentikäinen, O T, Heikkilä, P, Lundin, J, Joensuu, H, Bono, P, Ivaska, J
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 09.12.2010; Nature Publishing Group
• Subjects: 631/208/199; 631/45/612/1236; 631/80/84/2336; 692/699/67/1347; Amino Acid Sequence; Apoptosis; Biological and medical sciences; Breast cancer; Breast Neoplasms - metabolism; Breast Neoplasms - mortality; Breast Neoplasms - pathology; Cancer cells; Cell adhesion & migration; Cell Biology; Cell Line, Tumor; Cell migration; Cell Movement; Cell physiology; Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes; Collagen (type I); Collagen Type I - metabolism; Development and progression; Disease-Free Survival; Extracellular Matrix - chemistry; Fatty Acid Binding Protein 3; Fatty acid-binding protein; Fatty Acid-Binding Proteins - metabolism; Female; Fibronectin; Fibronectins - metabolism; Fundamental and applied biological sciences. Psychology; Growth; Gynecology. Andrology. Obstetrics; Health aspects; Human Genetics; Humans; Integrin alpha Chains - metabolism; Integrins; Internal Medicine; Mammary gland diseases; Medical prognosis; Medical sciences; Medicine; Medicine & Public Health; Metastases; Middle Aged; Molecular and cellular biology; Molecular Sequence Data; Neoplasm Invasiveness; Oncology; original-article; Physiological aspects; Prognosis; Protein interaction; Protein Interaction Domains and Motifs; Tumor cell lines; Tumors; Finland; migration; breast cancer; adhesion; invasion; integrin; MDGI; Breast disease; Growth; Migration; Breast cancer; Malignant tumor; Metastasis; Subunit; Adhesion; Carcinogenesis; Mammary gland diseases; Integrin; Inhibitor; Mammary gland; Cancer
• ISSN: 0950-9232; 1476-5594
• DOI: 10.1038/onc.2010.376

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.