AIR TOPIC 2 Cell- Matrix Adhesion and Cancer Description: Cell behaviour is determined by interactions within the microenvironment

generated in tissues. Cell adhesion is a fundamentally important process that influences cellular responses such as growth, survival, migration, differentiation and organi ation within multicellular structures. Cell adhesion to the basement membrane is necessary for cell survival and occurs via binding of specific cell surface adhesion receptors called !"ntegrins# to extracellular matrix proteins $%CM& such as laminin and collagen . During the onset of diseases such as cancer, the adhesive behaviour of cells is dramatically altered such that cells continue to grow in the absence of normal adhesive interactions, which involve changes in the function of integrins. 'his research topic will introduce cell adhesion, integrins and the role of these molecules in cancer progression. "t will demonstrate how basic scientific biomedical research can be translated into clinically useful technology of therapeutic value. (uestion ). Describe how integrins mediate cell-matrix attachment and how this process influences cell behaviour. Answer ). "ntegrins, cell surface adhesion receptors are responsible for cell-matrix attachment to the extracellular matrix by binding to short amino acid se*uences in extracellular matrix + collagen, fibronectin, laminin and distinct peptide se*uences- recognition se*uences. %.g. "ntegrins recogni e and bind to fibronectin, prototype of adhesion proteins- that lin, the matrix to one another and to cell surfaces. -econdly, integrins serve as anchors for the cytos,eleton to lin, to the extracellular matrix and thus causing stability of cell- matrix .unctions- focal adhesions and hemidesmosomes. 'hirdly, integrins facilitate cell-to-cell interactions. "ntegrins cluster to form focal complexes, which form focal adhesions by se*uential recruitment of talin, vinculin and alpha-actin, creating connections to actin cytos,eleton and subse*uently initiating actin bundle formation. 'his leads to development of tension at the point of adhesion, which allows formation of larger area of cell matrix adhesion and recruitment of signalling molecules to the cell .unctions. During cell migration, formation of new focal complexes results in the loss of tension at old focal adhesions, inactivating and dissociating integrin bound to the matrix. "ntegrins can reversibly bind matrix components because they are able to change conformation between active and inactive states. "nactive state integrins cannot bind to matrix, thus signals from the cytosol change the conformation of domains of integrins, extending head groups into the matrix and allow binding of the ligand. Cell responds to integrin binding by recruiting additional integrins, forming focal adhesion. /inally, integrins also act as signalling complexes in cells, relaying signals from the environment to regulate cell growth, movement, proliferation, migration and apoptosis.

(uestion 0. Describe briefly how integrins are involved in cancer highlighting the different stages and processes in which they are ,nown to play a role.

(uestion 1. "n what ways are integrins being targeted in the development of new medical technologies2 3ow is this lin,ed to their role in cancer2