Cancer cell response to extrinsic and intrinsic mechanical cue: Opportunities for tumor apoptosis strategies

Abstract Increasing studies have revealed the importance of mechanical cues in tumor progression, invasiveness, and drug resistance. During malignant transformation, changes manifest in either the mechanical properties of the tissue or the cellular ability to sense and respond to mechanical signals. The major focus of the review is the subtle correlation between mechanical cues and apoptosis in tumor cell from a mechanobiology perspective. To begin, we focus on the intracellular force, examining the mechanical properties of the cell interior, and outlining the role that the cytoskeleton and intracellular organelle-mediated intracellular forces play in tumor cell apoptosis. This paper also elucidates the mechanisms by which extracellular forces guide tumor cell mechanosensing, ultimately triggering the activation of the mechanotransduction pathway and impacting tumor cell apoptosis. Finally, a comprehensive examination of the present status of design and development of anti-cancer materials targeting mechanotransduction is presented, emphasizing the underlying design principles. Furthermore, the paper underscores the need to address several unresolved inquiries to enhance our comprehension of cancer therapeutics that target mechanotransduction.