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Updated: Feb 15, 2026
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A Time-lapse, Label-free, Quantitative Phase Imaging Study of Dormant and Active Human Cancer Cells
Published on: February 16, 2018
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c-Src activity is differentially required by cancer cell motility modes.
Jeremy S Logue1,2,3, Alexander X Cartagena-Rivera4, Richard S Chadwick4
1National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA. loguej@mail.amc.edu.
Oncogene
|January 31, 2018
Summary
Src signaling influences cancer cell migration modes. Inhibiting Src promotes blebbing, while leader bleb-based migration in confined spaces is resistant to Src inhibition, impacting metastasis inhibitor development.
Area of Science:
- Cell Biology
- Cancer Research
- Biophysics
Background:
- Cancer cell migration is crucial for metastasis and involves transitions between mesenchymal and ameboid modes.
- Environmental cues, such as extracellular matrix and confinement, dictate migration strategies.
- Understanding the signaling pathways that control these transitions is key for developing anti-metastasis therapies.
Purpose of the Study:
- To identify oncogenic signaling pathways regulating cancer cell migration transitions.
- To investigate the role of Src signaling in mediating mesenchymal-to-ameboid and leader bleb-based migration.
- To assess the potential of targeting Src for developing metastasis inhibitors.
Main Methods:
- Conducted a targeted screen using clinically relevant inhibitors to identify key signaling pathways.
- Utilized polydimethylsiloxane (PDMS) slabs to create confined microenvironments for cell migration studies.
- Analyzed actin dynamics, focal adhesion turnover, and cell mechanical properties.
Main Results:
- Elevated Src activity promoted amoeboid-like migration with membrane protrusions.
- Inhibition of Src led to focal adhesion disassembly and increased cell blebbing.
- Leader bleb-based migration in confined spaces was found to be resistant to Src inhibition.
- High Src activity altered actomyosin architecture and reduced cell mechanics, favoring leader bleb-based migration.
Conclusions:
- Src acts as a critical signal transducer influencing cancer cell migration mode transitions.
- Targeting Src may offer a strategy for inhibiting cancer cell metastasis, particularly in non-confined environments.
- The resistance of leader bleb-based migration to Src inhibition highlights the complexity of targeting cell migration in different physical contexts.
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