Related Experiment Video
Updated: Jun 14, 2026

Impedance-based Real-time Measurement of Cancer Cell Migration and Invasion
Published on: April 2, 2020
Integrin-linked kinase has a critical role in ErbB2 mammary tumor progression: implications for human breast cancer
S M Pontier1, L Huck, D E White
1Department of Medicine, McGill University, Montreal, Quebec, Canada.
Abstract:
Elevated expression of the integrin-linked kinase (ILK) has been observed in a variety of cancers and has been further correlated with poor clinical outcome. Here, we show that mammary epithelial disruption of ILK results in a profound block in mammary tumor induction. Consistent with these observations, inhibition of ILK function in ErbB2-expressing cells with small molecule inhibitor or RNA interference resulted in profound block in their in vitro invasive properties due to the induction of apoptotic cell death. The rare ILK-deficient tumors that eventually arose overcame this block in tumor induction by an upregulation of ErB3 phosphorylation. These observations provide direct evidence that ILK has a critical role in the initiation phase of ErbB2 tumor induction.
Insights
Integrin-linked kinase (ILK) is crucial for mammary tumor development. Inhibiting ILK blocks tumor growth and invasion, but tumors can overcome this by upregulating ErbB3 phosphorylation.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- Integrin-linked kinase (ILK) is frequently overexpressed in various cancers.
- Elevated ILK expression correlates with poor clinical outcomes in cancer patients.
Purpose of the Study:
- To investigate the role of ILK in mammary tumor induction and progression.
- To determine the effects of ILK inhibition on ErbB2-expressing cancer cells.
Main Methods:
- Mammary epithelial-specific disruption of ILK in a mouse model.
- Inhibition of ILK function using small molecule inhibitors and RNA interference in ErbB2-expressing cells.
- Analysis of tumor induction, cell invasion, and apoptotic cell death.
Main Results:
- Disruption of ILK in mammary epithelium significantly blocked tumor induction.
- ILK inhibition in ErbB2-expressing cells halted in vitro invasion by inducing apoptosis.
- Tumors that eventually developed in ILK-deficient settings upregulated ErbB3 phosphorylation to overcome the block.
Conclusions:
- ILK plays a critical role in the initiation phase of ErbB2-driven mammary tumor induction.
- Targeting ILK presents a potential therapeutic strategy for ErbB2-positive breast cancers.
- ErbB3 signaling is a compensatory mechanism for ILK-deficient tumors.
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Activation of Integrins
In "outside-in signaling," external factors in the extracellular space bind to exposed ligand binding sites on integrins. This causes the inactive protein to undergo a conformational change to become active. Integrins are often clustered on the cell membrane. Repetitive and regularly spaced ligand binding events provide an effective stimulus.

