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Current Cancer Drug Targets

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ISSN (Print): 1568-0096
ISSN (Online): 1873-5576

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Research Article

SULF1 Activates the VEGFR2/PI3K/AKT Pathway to Promote the Development of Cervical Cancer

Author(s): Juan Li, Xihao Wang, Zhilong Li, Minzhen Li, Xuelian Zheng, Danxi Zheng, Yanyun Wang* and Mingrong Xi*

Volume 24, Issue 8, 2024

Published on: 18 August, 2023

Page: [820 - 834] Pages: 15

DOI: 10.2174/1568009623666230804161607

Abstract

Background and Purpose: Sulfatase 1 (SULF1) can regulate the binding of numerous signaling molecules by removing 6-O-sulfate from heparan sulfate proteoglycans (HSPGs) to affect numerous physiological and pathological processes. Our research aimed to investigate the effect of the SULF1-mediated VEGFR2/PI3K/AKT signaling pathway on tumorigenesis and development of cervical cancer (CC).

Methods: The expression and prognostic values of SULF1 in patients with CC were analyzed through bioinformatics analysis, qRT-PCR, immunohistochemistry, and western blot. The function and regulatory mechanism of SULF1 in proliferation, migration, and invasion of cervical cancer cells were examined through lentivirus transduction, CCK8, flow cytometry analysis, plate colony formation assay, scratch assay, transwell assay, western blot, VEGFR2 inhibitor (Ki8751), and mouse models.

Results: SULF1 expression was significantly upregulated in CC tissues, which was significantly associated with poor prognosis of patients with CC. In vitro, the upregulation of SULF1 expression in HeLa cells promoted cell proliferation, colony formation, migration, and invasion while inhibiting apoptosis. Conversely, the downregulation of SULF1 expression had the opposite effect. In vivo, the upregulation of SULF1 expression resulted in a significant increase in both tumor growth and angiogenesis, while its downregulation had the opposite effect. Furthermore, western blot detection and cell function rescue assay confirmed that the upregulation of SULF1 in HeLa cells promoted the tumorigenic behaviors of cancer cells by activating the VEGFR2/PI3K/AKT signaling pathway.

Conclusion: SULF1 plays an oncogenic role in the tumorigenesis and development of CC, indicating its potential as a novel molecular target for gene-targeted therapy in patients with CC.

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