Due to the great therapeutic difficulties brought by the mechanical changes in the TME, emerging studies have focused on targeting the adverse mechanical factors in the TME to attenuate disease rather than conventionally targeting tumor cells themselves, which has been proven to be a potential therapeutic approach. However, far less understood is the comprehensive perspective of the functions and mechanisms of mechanotransduction. Tumor cells sense and respond to the strength, direction, and duration of mechanical cues in the TME by various mechanotransduction pathways. In this process, the tumor microenvironment (TME) fractures cellular and matrix architecture normality through biochemical and mechanical means, abetting tumorigenesis and treatment resistance. In this open structure the hybrid domain has swung outwards and the leg regions (not present) would be unbent so that the integrin is in an extended conformation, similar to that depicted in A.ĭynamic and heterogeneous interaction between tumor cells and the surrounding microenvironment fuels the occurrence, progression, invasion, and metastasis of solid tumors. (C) Ribbon diagram of the structure of the head region of integrin αIIbβ3 in complex with the high-affinity ligand eptifibatide (Xiao et al., 2004).

Some β-subunit domains are not visible in the structure.

The protein is in a closed form, which is bent at the knees or 'genu' (arrow). Metal ions (silver spheres) occupy the base of the propeller and the top face of the βA domain.

The α-subunit is shown in red, the β-subunit in blue peptide is shown as a ball-and-stick model with atoms in green. (B) Ribbon diagram of the structure of the ectodomain of integrin αVβ3 in complex with the high-affinity ligand cyclic RGD peptide (Xiong et al., 2002). The binding of ligands takes place at an interface between the propeller domain and βA domain. The overall structure is that of a head region supported on two legs that are made up of the calf1 and calf2 domains in the α-subunit and the EGF repeats and β-tail domain in the β-subunit. (A) Schematic diagram of integrin structure.

Macdown integring figure