Title:SULF1 Activates the VEGFR2/PI3K/AKT Pathway to Promote the
Development of Cervical Cancer
Volume: 24
Issue: 8
Author(s): Juan Li, Xihao Wang, Zhilong Li, Minzhen Li, Xuelian Zheng, Danxi Zheng, Yanyun Wang*Mingrong Xi*
Affiliation:
- Laboratory of Molecular Translational Medicine,
Center for Translational Medicine, Key Laboratory of Birth Defects and Related Diseases of Women and Children,
Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, 610041, Sichuan, China
- Department of Gynecology and Obstetrics, Key Laboratory of Birth Defects and Related Diseases of Women and Children,
Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, 610041, Sichuan,
China
Keywords:
SULF1, VEGFR2, Ki8751, cervical cancer, HeLa cells, heparan sulfate proteoglycans.
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.
