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Cancer Cell International
Published in: Cancer Cell International 1/2022

Open Access 01-12-2022 | Primary research

Annexin A1 promotes the progression of bladder cancer via regulating EGFR signaling pathway

Authors: Piao Li, Lingling Li, Zhou Li, Shennan Wang, Ruichao Li, Weiheng Zhao, Yanqi Feng, Shanshan Huang, Lu Li, Hong Qiu, Shu Xia

Published in: Cancer Cell International | Issue 1/2022

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Abstract

Background

Bladder cancer (BLCA) is one of the most common malignancies worldwide. One of the main reasons for the unsatisfactory management of BLCA is the complex molecular biological mechanism. Annexin A1 (ANXA1), a Ca2+-regulated phospholipid-binding protein, has been demonstrated to be implicated in the progression and prognosis of many cancers. However, the expression pattern, biological function and mechanism of ANXA1 in BLCA remain unclear.

Methods

The clinical relevance of ANXA1 in BLCA was investigated by bioinformatics analysis based on TCGA and GEO datasets. Immunohistochemical (IHC) analysis was performed to detect the expression of ANXA1 in BLCA tissues, and the relationships between ANXA1 and clinical parameters were analyzed. In vitro and in vivo experiments were conducted to study the biological functions of ANXA1 in BLCA. Finally, the potential mechanism of ANXA1 in BLCA was explored by bioinformatics analysis and verified by in vitro and in vivo experiments.

Results

Bioinformatics and IHC analyses indicated that a high expression level of ANXA1 was strongly associated with the progression and poor prognosis of patients with BLCA. Functional studies demonstrated that ANXA1 silencing inhibited the proliferation, migration, invasion and epithelial–mesenchymal transition (EMT) of BLCA cells in vitro, and suppressed the growth of xenografted bladder tumors in vivo. Mechanistically, loss of ANXA1 decreased the expression and phosphorylation level of EGFR and the activation of downstream signaling pathways. In addition, knockdown of ANXA1 accelerated ubiquitination and degradation of P-EGFR to downregulate the activation of EGFR signaling.

Conclusions

These findings indicate that ANXA1 is a reliable clinical predictor for the prognosis of BLCA and promotes proliferation and migration by activating EGFR signaling in BLCA. Therefore, ANXA1 may be a promising biomarker for the prognosis of patients with BLCA, thus shedding light on precise and personalized therapy for BLCA in the future.
Appendix
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Metadata
Title
Annexin A1 promotes the progression of bladder cancer via regulating EGFR signaling pathway
Authors
Piao Li
Lingling Li
Zhou Li
Shennan Wang
Ruichao Li
Weiheng Zhao
Yanqi Feng
Shanshan Huang
Lu Li
Hong Qiu
Shu Xia
Publication date
01-12-2022
Publisher
BioMed Central
Published in
Cancer Cell International / Issue 1/2022
Electronic ISSN: 1475-2867
DOI
https://doi.org/10.1186/s12935-021-02427-4

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