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

Abstract

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.

Keywords: ECM; anchorage-independence; mechanosensing; rigidity sensing; tumor stiffness.

Figure 1

The ‘yin and yang’ of cancer cell growth and mechanosensing. An illustration of the relationship between ECM rigidity and cell growth, where ‘yin’ (red) represents the cellular response to negative mechanical stimuli (e.g., a soft ECM), and ‘yang’ (blue) represents positive growth signals (see figure key). (A) In normal cells, the negative mechanical signals from a soft ECM are stronger than the positive signals, causing the cells to undergo anoikis. (B) In anchorage-independent transformed cells, the balance shifts and cells grow regardless of ECM rigidity.