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

Authors Lv Z, Li W, Wei X

Received 25 October 2018

Accepted for publication 16 April 2019

Published 3 July 2020 Volume 2020:13 Pages 6443—6452


Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Dr Sanjeev Srivastava

Zhonghua Lv,1 Wenlin Li,2 Xichao Wei3

1Department of Urology, Jining First People’s Hospital, Jining, Shandong 272011, People’s Republic of China; 2Department of Urology, Rizhao Traditional Chinese Medicine Hospital, Rizhao, Shandong 276800, People’s Republic of China; 3Department of Urology, Jining Traditional Chinese Medicine Hospital, Jining, Shandong 272000, People’s Republic of China

Correspondence: Xichao Wei
Department of Urology, Jining Traditional Chinese Medicine Hospital, No.3 West Huancheng Road, Jining, Shandong, People’s Republic of China
Tel +86 1 876 686 6536

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 β 1 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 β 1 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 β 1 up-regulation and focal adhesion kinase (FAK) phosphorylation. Furthermore, integrin β 1 inhibition led to decreased FAK phosphorylation and reduced tumor cell invasion. Overexpression of S100A9 increased xenograft tumor micro-metastases, integrin β 1 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 β 1/FAK through TLR4/NF-κB signaling leading to metastasis of prostate cancer cell.

Keywords: S100A9, prostate cancer, metastasis, integrin β 1, FAK

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