The 'Yin and Yang' of Cancer Cell Growth and Mechanosensing

Cells can sense their physical environment, or extracellular matrix (ECM), in a process called 'mechanosensing'. They do this via adhesion sites which allow them to attach to the ECM and to simultaneously obtain information about its mechanical properties. This mechanical information is converted to biochemical signals that affect cell behavior in various ways. Stiff surroundings tend to promote proliferation of normal cells, whereas soft substrates can lead to their death. Cancer cells, however, can survive on soft substrates, while maintaining increased proliferation on stiff surfaces. This observation is interesting because it suggests that cancer cells potentially ignore negative physical cues, such as a soft ECM, and exploit positive stimuli in the form of a stiff ECM. This brings to mind a 'yin and yang' equilibrium which is ever shifting in favor of cancer cell survival and growth. We propose that different rigidities, which cancer cells may encounter in different regions of the body, can lead to modifications in the interactions and adhesions of the cells with the ECM, thus activating signaling pathways that boost cancer cell proliferation. Here, we discuss these interactions through the lens of mechanosensing, and its abnormal function in cancer. In cancer, two unique and seemingly contradictory behaviors are evident: on the one hand, tumors are typically stiffer than the tissues in which they grow, and this high stiffness promotes their malignant progression; on the other hand, cancer cells are anchorage-independent-namely, they can survive and grow in soft environments that do not support cell attachment. How can these two features be consolidated? Recent findings on the mechanisms by which cells test the mechanical properties of their environment provide insight into the role of aberrant mechanosensing in cancer progression. In this review article, we focus on the role of high stiffness on cancer progression, with particular emphasis on tumor growth; we discuss the mechanisms of mechanosensing and mechanotransduction, and their dysregulation in cancerous cells; and we propose that a 'yin and yang' type phenomenon exists in the mechanobiology of cancer, whereby a switch in the type of interaction with the extracellular matrix dictates the outcome of the cancer cells.

Automated summary

Cells can sense the mechanical properties of their extracellular matrix through adhesion sites, converting this information into biochemical signals that affect cell behavior. Cancer cells respond differently to different stiffness substrates compared to normal cells, potentially leading to cancer progression.