Inward Tension of Talin and Integrin-related Osmotic Pressure are involved Synergetically in the Invasion and Metastasis of Non-small Cell Lung Cancer

Abstract

The integrin receptor protein talin plays vital roles in intracellular chemical and mechanical activities, and it is implicated in the high invasion and poor prognosis of non-small cell lung cancer (NSCLC). To better understand the mechanism underlying the function of talin in NSCLC invasion and metastasis, a few newly designed tension probe based on Förster resonance energy transfer was used for real-time observation of tension changes in A549 cells. High NSCLC cell aggressiveness was found to be accompanied with inward talin and outward glial fibrillary acidic protein (GFAP) tensions, which are closely associated with microfilament (MF) force and intracellular osmotic potential. The increased osmotic pressure resulted from the production of intracellular protein nanoparticles and the related ion influx. Furthermore, integrin activation was found to adjust the talin and GFAP tensions. Disruption of the interaction between talin and MFs blocked the mechanical source of talin, reducing both talin tension and osmotic pressure and thus inhibiting NSCLC cell invasion and migration. Consequently, our study demonstrates that talin is involved in NSCLC invasion and migration via its inward tension and that the integrin pathway is correlated closely with protein-nanoparticle-induced outward osmotic pressure.

Cancer associated talin point mutations disorganise cell adhesion and migration

“…Investigation of the contribution of talin to cancer progression is timely. During this study ~ 670 more cancer-associated talin-1 point mutations have been added to the COSMIC database ( Supplementary Fig.S1) and there are recent studies discussing the connection between talin and cancer 23,[55][56][57][58] . The work we present here demonstrates an efficient and fast pipeline approach using bioinformatics tools to characterise future talin mutations identified in cancer and other diseases.…”

Physical Forces in Glioblastoma Migration: A Systematic Review

“…A wide range of techniques have been employed to study oncotic and hydrostatic pressures in cancer. Different cancer studies have included adenocarcinoma [ 66 ], breast [ 67 ], colorectal [ 68 ], esophageal [ 69 ], head and neck [ 70 ], lung [ 71 ], melanoma [ 68 ], ovarian [ 72 ], prostate [ 73 ], and skin [ 74 ]. The variations in hyper- and hypo-osmotic states contributing to the tumorgenicity of the different cancers demonstrates the importance of regulating homeostasis.…”

Inflammasome-Induced Osmotic Pressure and the Mechanical Mechanisms Underlying Astrocytic Swelling and Membrane Blebbing in Pyroptosis

“…Astrocytic pyroptosis displays membrane blebbing, cell swelling, and further promotes pore formation on the astrocyte membrane, which exacerbates membrane permeabilization (5)(6)(7). Alterations of cell shape depend on cytoskeleton remodeling, which provides the cytoskeletal tractive forces against the outward osmotic pressure (OP) across the membrane (8)(9)(10). Our previous study suggested that the production of protein nanoparticles (PNs) in astrocytes upregulates cell osmolarity significantly by adsorbing cations and driving the influx of ions and water, thereby promoting cell swelling (8).…”