Extracellular fibrin promotes non-small cell lung cancer progression through integrin β1/PTEN/AKT signaling

Abstract

The extracellular matrix (ECM) has been strongly correlated with cancer progression in various tumor types. However, the specific mechanisms underlying ECM-associated tumor behaviors remain unclear. In this study, we found an enriched distribution of fibrin in tumor tissues obtained from high-grade non-small cell lung cancer (NSCLC) patients. For further investigation, we established an in vitro 3D culture system using fibrin gel and found that NSCLC cells grown in this system exhibited increased stemness and tumorigenesis. Mechanistically, we demonstrated that fibrin facilitated the activation of the phosphatase and tensin homolog (PTEN)/protein kinase B (AKT) signaling pathway through integrin β1. Furthermore, we found that blocking integrin β1 signals enhanced the tumor suppressive effects of chemotherapy, providing a novel approach for clinical therapy for NSCLC.

Local Production of Acute Phase Proteins: A Defense Reaction of Cancer Cells to Injury with Focus on Fibrinogen

“…Mainly fibroblasts produce the matrix and regulate matrix remodeling, but in cancer, the tumor matrix also originates from cancer cells [ 63 ]. An enriched distribution of fibrin in tumor tissues obtained from high-grade non-small cell lung cancer was demonstrated, and extracellular fibrin was associated with cancer progression, cancer stemness and chemotherapy resistance [ 64 ]. Thus, despite its relative under-representation, understanding the role of FN in the ECM is crucial, especially in contexts such as wound healing [ 65 ], inflammation, and tumor progression [ 64 ], where its presence and transient nature can significantly influence cell behavior and tissue dynamics [ 66 ].…”