How do integrins cause cancer?
Integrins in tumour cells. Integrins expressed in tumour cells contribute to tumour progression and metastasis by increasing tumour cell migration, invasion, proliferation and survival (see the figure). Integrin adhesion to the extracellular matrix (ECM) provides the traction required for tumour cell invasion.
What is integrin ligation?
Integrin ligation promotes receptor clustering and the formation of focal adhesions. Talin forms the initial contacts between integrin β-tails and the actin cytoskeleton. Vinculin crosslinks with Talin and actin to strengthen focal adhesions promoting focal adhesion growth.
What does the integrin receptor do?
Integrins are the principal receptors used by animal cells to bind to the extracellular matrix. A cell can regulate the adhesive activity of its integrins from within. Integrins also function as signal transducers, activating various intracellular signaling pathways when activated by matrix binding.
What are integrins in cancer?
Integrins are the main cellular adhesion receptors that through multifaceted roles as signalling molecules, mechanotransducers and key components of the cell migration machinery are implicated in nearly every step of cancer progression from primary tumour development to metastasis.
Is integrin a tumor suppressor?
Acting as oncogenes or tumor suppressor genes, integrins may be involved in the oncogenic transformation of normal cells and their growth into a primary tumor node.
What is selectin and integrin?
Selectins and some of their counter-receptors function also as signal-transducing receptors, significantly contributing to leukocyte and endothelial cell activation. Integrins represent a large family of adhesion receptors that are widely expressed and mainly interact with extracellular matrix components.
What is the function of integrin?
Integrins regulate cellular growth, proliferation, migration, signaling, and cytokine activation and release and thereby play important roles in cell proliferation and migration, apoptosis, tissue repair, as well as in all processes critical to inflammation, infection, and angiogenesis.
What causes angiogenesis?
The mechanism of blood vessel formation by angiogenesis is initiated by the spontaneous dividing of tumor cells due to a mutation. Angiogenic stimulators are then released by the tumor cells. These then travel to already established, nearby blood vessels and activates their endothelial cell receptors.
Is integrin a selectin?
Selectins comprise a family of three members (E-, P-, and L-selectin) that are differentially expressed by leukocytes and endothelial cells, and are involved in the early steps of leukocyte extravasation.
Is ICAM an integrin?
ICAM-1 is a ligand for LFA-1 (integrin), a receptor found on leukocytes.
How are integrins used in the fight against cancer?
This fact, together with the vital roles of integrins in cancer, has rendered integrins and integrin-dependent functions attractive therapeutic targets in the fight against cancer (part f ).
How are integrin activation and inactivation counterbalanced?
Integrin activation can be counterbalanced by inactivating proteins such as integrin cytoplasmic domain-associated protein 1 (ICAP-1; also known as ITGB1BP1), filamin A, SHARPIN and proteins of the SH3 and multiple ankyrin repeat domains (SHANK) family, which, directly or indirectly, restrict the ability of talin to bind and activate integrins 16]
How are Integrins involved in the metastatic cascade?
For most solid tumours, the metastatic cascade begins with cancer cells breaching the underlying basement membrane. This process is considered to require proteolytic activity, and integrins contribute by upregulating the expression of matrix metalloproteinase genes and facilitating protease activation and function at the ECM interface 18.
What is the role of integrins in the ECM?
Integrins are unique multidirectional signalling molecules (Box 1 ). Integrin activation and binding to the ECM trigger the recruitment of the so-called adhesome: a complex array of signalling, scaffolding and cytoskeletal proteins engaging directly or indirectly with integrin cytoplasmic tails 5, 6, 7.