Integrins in development and cancer

Abstract

The correct control of cell fate decisions is critical for metazoan development and tissue homeostasis. It is established that the integrin family of cell surface receptors regulate cell fate by mediating cell-cell and cell-extracellular matrix (ECM) interactions. However, our understanding of how the different family members control discrete aspects of cell biology, and how this varies between tissues and is temporally regulated, is still in its infancy. An emerging area of investigation aims to understand how integrins translate changes in tension in the surrounding microenvironment into biological responses. This is particularly pertinent due to changes in the mechanical properties of the ECM having been linked to diseases, such as cancer. In this review, we provide an overview of the roles integrins play in important developmental processes, such as proliferation, polarity, apoptosis, differentiation and maintenance of "stemness". We also discuss recent advances in integrin mechanobiology and highlight the involvement of integrins and aberrant ECM in cancer.

Keywords: Cancer; Cell fate; Extracellular matrix; Integrins; Mechanobiology; Stem cells.

Fig. 1

The role of integrins in cell fate. Integrins are unique in their ability as transmembrane receptors that control cell fate decisions such as whether a cell should undergo proliferation, apoptosis or differentiation, or become polarised. The cellular context also influences these cell fate decisions, with integrins acting as sensors that communicate information from the surrounding microenvironment [extracellular matrix (ECM)] to the cell

Fig. 2

Tensile strength and cell fate of the ECM. The increasing rigidity of tissue can have dramatic effects on cell fate. In normal embryonic stem cells the rigidity of the matrix they are exposed to can influence their cell fate, with the resulting cells becoming either neurogenic (brain), myogenic (muscle) or osteogenic (bone) with increasing matrix stiffness, respectively. In cancer, increasing matrix rigidity leads to increased deposition of ECM components (collagen I & V) as well as increased degradation to help facilitate tumour growth. The increased ECM stiffness results in increased recruitment of integrins to focal adhesions, the upregulation of downstream integrin signalling pathways and increased Rho kinase (ROCK) activation, resulting in proliferation and cell survival