Mutant cadherin affects epithelial morphogenesis and invasion, but not transformation

Area of Science:

• Cell Biology
• Molecular Biology
• Cancer Research

Background:

• E-cadherin is crucial for cell adhesion and tissue integrity.
• Altered E-cadherin expression is linked to tumor progression and invasion.
• Understanding cadherin's role in invasion versus transformation is critical.

Purpose of the Study:

• To investigate the functional consequences of expressing mutant E-cadherin with a large extracellular deletion in MDCK cells.
• To determine if impaired cadherin adhesion induces cellular transformation or an invasive phenotype.
• To assess the relevance of these findings to human tumor progression, especially with E-cadherin mutations.

Main Methods:

• Engineering MDCK cells to express mutant E-cadherin with reduced endogenous cadherin levels.
• Culturing cells in collagen gels to form cysts and assessing response to hepatocyte growth factor/scatter factor (HGF/SF).
• Evaluating anchorage-independent growth in soft agar and cell proliferation rates.

Main Results:

• Mutant E-cadherin overexpression significantly reduced endogenous E- and K-cadherin expression, decreasing cell adhesion.
• Cells formed cysts and responded to HGF/SF with tubule extension, but exhibited shedding from cyst walls.
• Despite invasiveness, cells did not display anchorage-independent growth or increased proliferation, indicating no transformation.

Conclusions:

• Cadherin loss induces an invasive phenotype, a late stage of tumor progression, without causing cellular transformation.
• These findings are particularly relevant for understanding tumor progression in cancers with altered E-cadherin, including those with extracellular domain mutations.