What is it about?

“Watch out, shark!” Your response to someone yelling this while you sit at your office desk would be very different than if you had been swimming in the ocean. Just like we respond to cues based on our environment, so do cells, and cancer cells are particularly good at adjusting to environmental changes. However, little is known about how cancer cells connect environmental changes to cellular communication in order to thrive in changing environments. One of these environmental changes is the stiffness of the material that surrounds the cells. In this study we identify a pathway that connects the properties of the extracellular matrix to signals that control cell mobility/motility. Focal adhesions are specialized structures that form a link between the external environment and internal machinery of the cell. Previous work from our lab found that, unexpectedly, the signaling protein PKA is a component of focal adhesions. This new body of work shows that PKA interacts with the protein talin to integrate external cues into internal cellular communication. Talin is a critical component of the mechanical interactions between cells and their environment. This new work highlights how, as cells pull against the extracellular matrix, the tension exerted results in the stretching of talin and subsequent interaction with PKA. This novel integration between the external environment and talin serves as a signaling complex that couples the sensing of external cues with cellular communication.

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Why is it important?

As tumors grow, the surrounding extracellular matrix remodels, thickens, and stiffens. Cancer cells respond to these environmental changes by growing more rapidly, becoming more mobile and invasive, and increasing defenses to avoid cell death. However, little is known about how cancer cells integrate environmental circumstances into cellular changes that promote growth, mobility, and survival. This study establishes a pathway between extracellular changes and intracellular communication. Future work will explore how changing the interactions between components of this pathway affect cell motility and invasion potentially leading to new therapeutic targets.

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This page is a summary of: The focal adhesion protein talin is a mechanically gated A-kinase anchoring protein, Proceedings of the National Academy of Sciences, March 2024, Proceedings of the National Academy of Sciences,
DOI: 10.1073/pnas.2314947121.
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