Cell Migration Dynamics in Cancer Metastasis

Cancer metastasis relies on the ability of malignant cells to migrate from the primary tumour, invade surrounding tissues and colonise distant organs. This process involves complex interactions between the cytoskeleton, cell–cell junctions and the extracellular matrix. Tumour cells adopt distinct migration modes, most notably mesenchymal migration driven by elongated morphology and proteolytic degradation of the matrix, and amoeboid migration characterised by rounded shape and actomyosin contractility. Plasticity between these modes allows cancer cells to adapt to varying mechanical constraints and biochemical cues within the microenvironment. Key regulators include Rho GTPase signalling, integrin-mediated adhesion, metabolic sensors such as AMP-activated protein kinase and secreted factors that remodel the matrix. Mitochondrial dynamics and energy production further influence migratory efficiency, while biochemical signals such as WNT and TGF-β modulate transcriptional programmes that sustain invasive behaviour. Understanding the interplay between mechanical forces, metabolic state and biochemical signalling is essential for developing targeted therapies to impede metastatic dissemination.

Research from Nature Portfolio

Recent work has identified AMP-activated protein kinase as a mechano-metabolic sensor that couples adhesion sensing with mitochondrial fission and cytoskeletal remodelling. High AMPK activity in low-adhesion, amoeboid cells induces mitochondrial fragmentation and activates myosin II-driven contractility, promoting efficient rounded-amoeboid migration. Inhibition of AMPK in vivo reduces metastatic potential, highlighting a metabolic vulnerability. Another study has elucidated a WNT11-FZD7-DAAM1 axis that activates Rho-ROCK-myosin II signalling in melanoma, linking invasive amoeboid behaviour with tumour-initiating capacity. Amoeboid melanoma cells co-express proliferation and invasion programmes, and are enriched at invasive fronts and metastatic lesions, suggesting that targeting this signalling cascade may reduce residual disease after surgery.

Cell Migration Dynamics in Cancer Metastasis publication trend

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

Technical terms

Amoeboid migration: A mode of cell movement characterised by rounded morphology and high actomyosin contractility that enables cells to squeeze through the matrix without extensive proteolysis.

Mesenchymal migration: Migration driven by elongated cell shape, integrin-based adhesion and focal proteolytic degradation of the extracellular matrix.

Extracellular matrix (ECM): A network of proteins and polysaccharides that surrounds cells, providing structural support and biochemical signals.

Actomyosin contractility: Force generation within cells arising from the interaction of actin filaments and myosin motors, essential for cell shape changes and movement.

Rho GTPase signalling: A family of molecular switches that regulate cytoskeletal dynamics, adhesion and cell polarity during migration.

References

1. AMPK is a mechano-metabolic sensor linking cell adhesion and mitochondrial dynamics to Myosin-dependent cell migration. Nature Communications (2023).
2. WNT11-FZD7-DAAM1 signalling supports tumour initiating abilities and melanoma amoeboid invasion. Nature Communications (2020).
3. Matrix Resistance Toward Proteolytic Cleavage Controls Contractility‐Dependent Migration Modes During Angiogenic Sprouting. Advanced Science (2024).
4. Engine shutdown: migrastatic strategies and prevention of metastases. Trends in Cancer (2023).
5. Modes of invasion during tumour dissemination. Molecular Oncology (2016).