Impact of mechanical property alterations on cancer cell motility and metastasis

Extensive research has highlighted the pivotal roles of extracellular matrix (ECM) mechanics and actin cytoskeleton dynamics in regulating cancer progression and metastasis. Mechanical cues from the ECM govern cell motility, proliferation, and invasiveness through mechanotransduction pathways that translate physical stimuli into biochemical signals. A central downstream response is the reorganization of actin filaments, which controls cell shape, force generation, and migration.

This review aims to clarify how ECM stiffness and cellular mechanical properties jointly shape cancer cell behavior, with particular emphasis on motility and mechanotransduction.

As tumors progress, a "mechanical paradox" emerges, namely the ECM becomes progressively stiffer, while cancer cells often display reduced stiffness compared with their normal counterparts. Recent studies reinterpret this phenomenon as a form of dynamic reciprocity, in which cancer cells actively remodel their surrounding ECM through bidirectional mechanical feedback loops. These concurrent but opposing mechanical alterations have been linked to metastatic potential, yet their combined impact on the dynamic properties of cancer cells remains poorly understood. This review synthesizes current findings on the influence of ECM stiffness, cellular elasticity, and cytoskeletal remodeling on cancer cell motility and mechanotransduction.

By integrating insights into ECM mechanics and cellular elasticity, this review highlights how reciprocal mechanical interactions between cancer cells and their microenvironment contribute to metastatic progression. Understanding this interplay will be crucial for developing more accurate mechanobiological models and identifying new mechanotherapeutic strategies.