Figure 3: Mechanically induced tumour cell biophysical adaptations acquired in the primary tumour and retained in the distant organ foster extravasation, avoidance of dormancy, and secondary site colonization.

We propose that biophysical adaptations acquired by tumour cells in the primary site are retained at the secondary site via mechanical memory and facilitate the later steps of metastasis. Extravasation can be enhanced by memory-induced retention of increased integrin β1 signalling, secretion of matrix-modifying enzymes and pro-angiogenic factors, fast migration, high traction forces, and optimal tumour cell stiffness. Dormancy avoidance can be facilitated by maintenance of increased integrin β1 signalling, promoting faster proliferation. Colonization can be enhanced by retention of increased tumour cell stemness, resistance to apoptosis, secretion of growth factors, cytokines, and matrix-remodelling enzymes, and increased proliferation.