Cancer invasion plasticity during the metastatic cascade: strategies to survive and thrive

The metastatic process is largely inefficient, yet its outcome - the dissemination of cancer cells from the primary tumor to distant sites and the formation of metastases - remains the leading cause of cancer-related death. The individual steps of the metastatic cascade impose major challenges and represent bottleneck steps, eliminating the majority of cancer cells along the way. To overcome these barriers, cancer cells must adapt to diverse environments, ranging from confining spaces to fluid, non-adhesive milieus. Distinct invasion strategies, including collective, mesenchymal and amoeboid, confer specific advantages under such conditions. Cancer cells capable of exploiting features of the invasion modes by switching among them are more likely to survive and thrive throughout all steps of the metastatic cascade. Thus, invasion plasticity represents a key adaptive strategy enabling cancer cells to endure metastatic progression. In this review, we concisely summarize the contribution of collective, mesenchymal and amoeboid invasion features during individual steps of the metastatic cascade, highlight evidence that invasion plasticity fuels metastatic dissemination and discuss how targeting such adaptability may reduce metastatic burden.