Inositol polyphosphate multikinase is a metformin target that regulates cell migration.

Area of Science:

• Cell Biology
• Biochemistry
• Pharmacology

Background:

• Metformin exhibits antitumor properties, potentially linked to altered cell adhesion protein expression.
• Inositol polyphosphate multikinase (IPMK) role in cell adhesion and migration is not fully understood.

Purpose of the Study:

• To investigate the role of IPMK in regulating cell adhesion and migration.
• To determine if IPMK is a metformin target and its downstream effects on integrin expression.

Main Methods:

• Treatment of murine cells (myocytes, adipocytes, hepatocytes) with metformin.
• Analysis of IPMK knockout (IPMK-/-) mouse embryonic fibroblast cells.
• Nanonet force microscopy to measure cell adhesion and contractility.
• Pharmacological inhibition of focal adhesion kinase (FAK) and proline-rich tyrosine kinase 2.

Main Results:

• Metformin down-regulated integrin β1 and IPMK in murine cells.
• IPMK deficiency reduced integrin β1 and β3 gene expression, increasing FAK activity and Rho/Rac/Cdc42 levels, leading to migration defects.
• Reduced cell adhesion and contractility forces were observed.
• FAK inhibition partially restored integrin β1 expression.

Conclusions:

• IPMK is a metformin target involved in regulating cell migration.
• The IPMK-integrin β1 pathway is crucial for cell adhesion and contractility.
• This pathway provides a potential link between metformin use and impaired wound healing.