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Updated: Jun 9, 2026

Isolation of Intact, Whole Mouse Mammary Glands for Analysis of Extracellular Matrix Expression and Gland Morphology
Published on: October 30, 2017
Mammary-derived growth inhibitor (MDGI) interacts with integrin α-subunits and suppresses integrin activity and
1Medical Biotechnology, VTT Technical Research Centre of Finland, Turku, Finland.
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.
Insights
Mammary-derived growth inhibitor (MDGI) binds to integrin alpha-subunits, inhibiting cancer cell migration and invasion. MDGI expression in breast cancer patients correlates with better survival, suggesting a role in favorable prognosis.
Area of Science:
- Oncology
- Cell Biology
- Biochemistry
Background:
- Cancer metastasis, driven by cell migration and invasion, is a major cause of mortality.
- Integrin heterodimers mediate cell adhesion, crucial for migration and invasion processes.
- While β1-integrin interactions are understood, regulatory partners for α-subunit cytoplasmic tails remain largely unknown.
Purpose of the Study:
- To identify and characterize novel binding partners for integrin α-subunit cytoplasmic tails.
- To investigate the functional role of mammary-derived growth inhibitor (MDGI) in integrin activity and breast cancer progression.
Main Methods:
- Direct binding assays to confirm MDGI interaction with integrin α-subunits.
- Analysis of integrin conformation and adhesion in breast cancer cell lines with varying MDGI expression.
- Assessment of cell migration and invasion assays.
- Retrospective analysis of MDGI expression in patient tumor tissue microarrays.
Main Results:
- MDGI directly binds to integrin α-subunit cytoplasmic tails, inhibiting integrin activity.
- MDGI expression suppresses the active conformation of integrins, reducing adhesion to collagen and fibronectin.
- MDGI expression significantly inhibits breast cancer cell migration and invasion.
- Patients with MDGI-positive tumors exhibited more favorable 10-year distant disease-free survival.
Conclusions:
- MDGI is a novel interacting partner for integrin α-subunits, modulating integrin activity.
- MDGI expression suppresses breast cancer cell invasion and is associated with a favorable prognosis.
- MDGI represents a potential therapeutic target for reducing breast cancer metastasis.
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