Title:ADGRL4 Promotes Cell Growth, Aggressiveness, EMT, and Angiogenesis in Neuroblastoma via Activation of ERK/STAT3 Pathway
Volume: 25
Issue: 1
Author(s): Geng Geng, Lei Zhang, Ying Yu, Xingqing Guo, Qinghao Li and Ming Ming*
Affiliation:
- Department of Pediatric Surgery, The Affiliated Taian City Central Hospital of Qingdao University, Taian,
271000, Shandong Province, P.R. China
Keywords:
ADGRL4, ERK/STAT3 signaling pathway, neuroblastoma, cell growth, angiogenesis, cancer-related deaths.
Abstract:
Background: Neuroblastoma (NB) is one of the most common pediatric
solid tumors. Emerging evidence has indicated that ADGRL4 can act as a master
regulator of tumor progression. In addition, it is well documented that the ERK/STAT3
signaling pathway can promote the proliferation, EMT, angiogenesis, and metastasis in
tumors. The current study was formulated to elucidate the exact role of ADGRL4 in the
malignant behaviors of NB cells and to investigate the intrinsic mechanism.
Methods: In this work, expression differences of ADGRL4 in human NB cell lines and
HUVECs were assessed via RT-qPCR and western blot analysis. For functional
experiments, sh-ADGRL4 was transfected into SK-N-SH cells to generate ADGRL4
knockdown stable cell line. Moreover, ADGRL4 knockdown stable SK-N-SH cells were
treated with LM22B-10 (an ERK activator) for rescue experiments. CCK-8, colony
formation, would healing, and transwell assays determined NB cell growth, migration,
and invasion. Meanwhile, proliferation-, metastasis- and EMT- associated proteins
were also detected. Additionally, a tube formation assay was employed to evaluate in
vitro angiogenesis. VM-cadherin, the marker of angiogenesis, was assessed using
immunofluorescence staining.
Results: Data showed notably upregulated ADGRL4 in NB cells, especially in SK-NSH
cells. ADGRL4 knockdown inhibited NB cell growth, migration, invasion, EMT, and
in vitro angiogenesis. ADGRL4 knockdown inactivated ERK/STAT3 signaling pathway.
Activation of the ERK/STAT3 signaling pathway partially rescued the tumor
suppression effects of ADGRL4 knockdown on NB cells.
Conclusion: To conclude, the downregulation of ADGRL4 may inhibit cell growth,
aggressiveness, EMT, and angiogenesis in NB by inactivating the ERK/STAT3
signaling pathway.
