<p>S100A9 promotes prostate cancer cell invasion by activating TLR4/NF-κB/integrin β1/FAK signaling</p>

Abstract

Background: S100A9, which is expressed in prostate cancer, has been reported in association with prostate cancer progression. However, the role of S100A9 in prostate cancer metastasis is largely unknown. The aim of this study was to investigate the effect of S100A9 on prostate cancer cell invasion and the involved mechanisms. Materials and methods: Integrin β1 expression in PC-3 and DU-145 cells was determined by quantitative real-time polymerase chain reaction (PCR) (qRT-PCR) and Western blot. Cellular invasion was measured by transwell invasion assay. Western blot was used to determine protein expression. Concentrations of S100A9 and fibronectin were analyzed by enzyme-linked immunosorbent assay. The protein interaction was detected by immunoprecipitation. The NF-κB activity was measured by luciferase reporter assay. The DU-145 cells metastasis in vivo was determined in mice xenograft models after S100A9 overexpression. Results: S100A9 promoted prostate cancer cells invasion, integrin β1 expression and fibronectin secretion. Further investigation evidenced that S100A9 interacted with Toll-like receptor 4 (TLR4) and activated NF-κB, which was responsible for tumor cell invasion, integrin β1 up-regulation and focal adhesion kinase (FAK) phosphorylation. Furthermore, integrin β1 inhibition led to decreased FAK phosphorylation and reduced tumor cell invasion. Overexpression of S100A9 increased xenograft tumor micro-metastases, integrin β1 expression and induced NF-κB and FAK activation in vivo. Conclusion: Our study demonstrated that S100A9 promotes prostate cancer cell invasion, and one of the underlying molecular mechanisms is that S100A9 activates integrin β1/FAK through TLR4/NF-κB signaling leading to metastasis of prostate cancer cell.

Human RAD51 Protein Forms Amyloid-like Aggregates In Vitro

“…It was suggested that SAA may enhance cancer cell proliferation and migration through the regulation of inflammation [ 62 , 63 ]. The amyloid protein S100A9, which is one of key factors promoting neuroinflammation [ 64 ], plays a role in prostate cancer invasion and is associated with disease progression [ 65 ]. This amyloidogenic protein was also found to be up-regulated in other cancers, including breast cancer, colon cancer, hepatocellular carcinoma, gastric cancers and others [ 66 ].…”

Role and correlation of exosomes and integrins in bone metastasis of prostate cancer

“…They link extracellular ligands to intracellular signal transduction through global conformational changes: when the extracellular domain undergoes global conformational changes, its binding affinity to extracellular ligands is greatly increased; At the same time, the ligand binding to the extracellular domain can stably maintain a high‐affinity conformation to achieve intracellular signal transmission, thereby altering cell functions, including proliferation, metabolism, and metastasis (Park et al, 2020). Integrin‐mediated alterations in cell function perform an integral function in numerous pathological changes, including in the metastatic process of cancer cells (Lv et al, 2020). Multiple research reports have confirmed that integrins are strongly linked to PCa metastasis, which participates in a variety of interconnected cell pathways and contributes to the growth and metastasis of PCa cells (Salemi et al, 2021).…”

The Etiology and Pathophysiology Genesis of Benign Prostatic Hyperplasia and Prostate Cancer: A New Perspective

“…Hypoxia and the hypoxia inducible factor 1increases S100A8/A9 expression in prostate cancer [130] and is considered an early carcinogenesis event [131][132][133]. It has been demonstrated that S100A9 promotes prostate cancer cell invasion [134]. The p53 mutants can form amyloid-like structures that accumulate in cells [135].…”