Cell Migration and Protein Kinase Signaling in Cancer

Cancer cell migration is a multistep process that underpins invasion and metastasis, involving dynamic remodelling of the actin–myosin cytoskeleton, adhesion to and detachment from the extracellular matrix, and directed cell movement. Central to these events are protein kinases that translate extracellular cues into coordinated intracellular responses. Serine/threonine kinases such as Rho-associated coiled-coil kinases (ROCKs), myotonic dystrophy-related Cdc42-binding kinases (MRCKs), p21-activated kinases (PAKs) and atypical protein kinase C isoforms regulate the assembly of focal adhesions, the formation of lamellipodia and filopodia, and the contractile forces that propel cells forwards. Equally, the cyclic AMP-dependent protein kinase A (PKA) and other AGC-family kinases impose spatially restricted signalling niches that fine-tune protrusion and retraction cycles. Dysregulation of these pathways, whether through overexpression, mutation or aberrant localisation of kinases or their upstream regulators such as Rho GTPases, drives a pro-migratory phenotype in carcinoma and sarcoma cells. The elucidation of kinase-substrate networks, aided by advances in chemical biology and high-resolution imaging, has revealed potential vulnerabilities that can be exploited by selective small-molecule inhibitors. Such targeted agents promise to interfere with tumour dissemination and to complement existing cytotoxic therapies, offering a route towards metastasis-directed intervention in clinical oncology.

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Cell Migration and Protein Kinase Signaling in Cancer publication trend

The graph below shows the total number of articles in cell migration and protein kinase signaling in cancer across all publications each year (not limited to Nature Index journals).

Technical terms

Protein kinase: An enzyme that covalently attaches phosphate groups to specific amino acids in substrate proteins, modulating their activity, localisation or interactions.

Rho GTPase: A family of small G-proteins that cycle between active and inactive states to regulate actin dynamics, cell polarity and adhesion.

Actin–myosin cytoskeleton: A network of actin filaments and motor proteins whose coordinated contraction and polymerisation drive cell shape changes and motility.

Focal adhesion: A multiprotein complex that links the extracellular matrix to the actin cytoskeleton and transduces mechanical and chemical signals.

Lamellipodium: A thin, sheet-like membrane protrusion formed by branched actin polymerisation at the leading edge of migrating cells.

Metastasis: The process by which cancer cells disseminate from a primary tumour to establish secondary lesions in distant organs.

References

1. Opportunities and Challenges for the Development of MRCK Kinases Inhibitors as Potential Cancer Chemotherapeutics. Cells (2023).
2. Targeting Rho GTPase Signaling Networks in Cancer. Frontiers in Cell and Developmental Biology (2020).
3. Protein Kinase A in cellular migration—Niche signaling of a ubiquitous kinase. Frontiers in Molecular Biosciences (2022).
4. The actin-myosin regulatory MRCK kinases: regulation, biological functions and associations with human cancer. Journal of Molecular Medicine (2014).
5. A novel small-molecule MRCK inhibitor blocks cancer cell invasion. Cell Communication and Signaling (2014).