The Adhesome Network: Key Components Shaping the Tumour Stroma

SIMPLE SUMMARY: Tumours are not formed only by malignant cells but contain many other cell types, including endothelial and mural cells of blood vessels, immune cells and cancer-associated fibroblasts. These host cells, together with extracellular matrix, form the tumour stroma. Tumour growth and metastasis depends on interactions between cancer cells and tumour stroma. Cell adhesion to extracellular matrix is essential for tissue growth and homeostasis and is deregulated in many pathological conditions, including cancer. This review highlights the vital role of cell adhesion in malignancy and describes how adhesion components regulate tumour stroma responses and control cancer development. ABSTRACT: Beyond the conventional perception of solid tumours as mere masses of cancer cells, advanced cancer research focuses on the complex contributions of tumour-associated host cells that are known as “tumour microenvironment” (TME). It has been long appreciated that the tumour stroma, composed mainly of blood vessels, cancer-associated fibroblasts and immune cells, together with the extracellular matrix (ECM), define the tumour architecture and influence cancer cell properties. Besides soluble cues, that mediate the crosstalk between tumour and stroma cells, cell adhesion to ECM arises as a crucial determinant in cancer progression. In this review, we discuss how adhesome, the intracellular protein network formed at cell adhesions, regulate the TME and control malignancy. The role of adhesome extends beyond the physical attachment of cells to ECM and the regulation of cytoskeletal remodelling and acts as a signalling and mechanosensing hub, orchestrating cellular responses that shape the tumour milieu.