**2. Integrins**

Integrins are heterodimeric transmembrane proteins responsible for mediating cell-cell and cell-extracellular matrix (ECM) interactions. These proteins bind to ECM ligands such as fibronectin, collagen, laminin, nidogen, vitronectin and other adhesion molecules such as ICAM-1. In healthy tissues, integrins play a key role in hemostasis, cell survival, migration, and proliferation; while in pathological processes, these receptors are associated with angiogenesis, inflammatory activity, osteoporosis and metastasis [11–13].

Integrins are homo- or hetero-dimeric proteins of α and β subunits combination. So far, 18 α-subunits and 8 non-covalently bound β-subunits combined constitute 24 types of integrins [13, 14]. The majority of integrins recognize the Arg-Gly-Asp (RGD) sequence present in essential ECM proteins. It has been shown that the modulation of residues flanking the RGD sequence may be the mechanism that regulates the specificity of integrin-ligand interactions [15, 16]. Each integrin binds to one or more ligands [17].

Some examples are integrins like α5β1, α4β1 and αvβ3 that have an affinity to fibronectin; α1β1 and α2β1 recognize collagen; αvβ3 and αvβ5 can bind to vitronectin and fibrinogen and, α2β1, α3β1 and α6β1 exerts activity on laminin [18]. Besides, αIIbβ3 expressed in platelets bind fibrinogen or von Willebrand factor that contribute to platelet aggregation [19]. Additionally, some integrins interact with cell receptors such as α4β1 and α9β1 that binds to VCAM-1 (Vascular cell adhesion molecule-1) and α4β1 to mucosal vascular addressin cell adhesion molecule-1 (MadCAM-1) [18, 20].

Integrins transduce signals (from the outside to the inside of the cell and vice versa) mediated by the extracellular environment; ligand binding leads to conformational changes allowing the integrin to produce signals for cells to migrate, proliferate or undergo apoptosis [21, 22]. Integrins have three conformational states that depend on the regulation of the adaptor proteins and the traction force of the cytoskeleton at the time the integrins bind their ligands. The open extended form indicates a high affinity for the ligand, when ligand binds triggers activation of the signaling pathway [23], whereas the closed folded or closed extended form has a low affinity for the ligand [14].

In normal tissues, integrins have checkpoints over cell proliferation, however, integrin expression is altered in cancer. Such is the case of αvβ3, integrin overexpressed in tumor cells which can promote cell migration and angiogenesis. In concert with αvβ5, these integrins contribute to drug resistance and radiotherapy. Invasion and metastasis occur when a cancer cell escapes from the primary tumor, invades, survives in the bloodstream, and colonizes distant sites. Integrins influence these processes by modulating the colonization of metastatic sites and leading to anchorage-independent survival of tumor cells. Integrins have been associated with high rates of metastasis and poor prognosis in different types of cancers [23].

*A Systematic Review of the Pharmacological Potential of Disintegrins on Breast Cancer DOI: http://dx.doi.org/10.5772/intechopen.105162*
