Abstract
Aims and hypothesisEpidermal growth factor (EGF) has been shown to induce the migration of various cancer cells. However, the underlying signaling mechanisms for EGF-induced migration of oral squamous cell carcinoma (OSCC) remain to be elucidated. WNT7A, a member of the family of 19 Wnt secreted glycoproteins, is commonly associated with tumor development. It is mostly unknown whether and, if so, how EGF modulates WNT7A in OSCC cells. The role of WNT7A in OSCC was thus investigated to explore the underlying signaling mechanisms for EGF-induced migration of OSCC.MethodsCell migration was measured by Wound healing assay and Transwell assay. Western blotting was carried out to detect the expression of WNT7A, MMP9, β-catenin, p-AKT, and p-ERK. The cells were transfected with plasmids or siRNA to upregulate or downregulate the expression of WNT7A. The location of β-catenin was displayed by immunofluorescence microscopy. Immunohistochemistry was carried out to confirm the relation between WNT7A expression and OSCC progression.ResultsThe present study showed that the levels of WNT7A mRNA and protein were increased by EGF stimulation in OSCC cells. Besides, it was proved that p-AKT, but not p-ERK, mediated the expression of WNT7A protein induced by EGF. Furthermore, the inhibition of AKT activation prevented the EGF-induced increase of WNT7A and matrix metallopeptidase 9 (MMP9) expression and translocation of β-catenin from the cytoplasm to the nucleus. Moreover, histological analysis of OSCC specimens revealed an association between WNT7A expression and poor clinical prognosis of the disease.ConclusionsThe data in this paper indicated that WNT7A could be a potential oncogene in OSCC and identified a novel PI3K/AKT/WNT7A/β-catenin/MMP9 signaling for EGF-induced migration of OSCC cells.
Highlights
It is well known that Wnt signaling is one of the most important pathways, playing an essential role in a variety of cellular processes (Ghosh et al, 2019; Goldsberry et al, 2019; Sharon et al, 2019)
The results of this study clearly demonstrate a unique relationship between EGF signaling and WNT7A expression in regulating cancer cell migration, which could be essential in the identification of therapeutic targets for the treatment of oral squamous cell carcinoma (OSCC)
The results showed that treatment with EGF did not noticeably affect the viability of CAL27 cells (Figure 1B). qPCR was applied to detect the mRNA expression of all members of the Wnt gene family in CAL27 and HSC3 cells (Figures 1C, D)
Summary
It is well known that Wnt signaling is one of the most important pathways, playing an essential role in a variety of cellular processes (Ghosh et al, 2019; Goldsberry et al, 2019; Sharon et al, 2019). The Wnt/b-catenin pathway, known as the canonical Wnt signaling, controls cell growth, differentiation, apoptosis, and self-renewal (Rosenbluh et al, 2012; Gonzalez-Moles et al, 2014; Nusse and Clevers, 2017; Alamoud and Kukuruzinska, 2018) This pathway is aberrantly activated during the development of multiple cancers and can coordinate with other pathways to regulate cancer cell proliferation, migration, and invasion (Yu et al, 2012; Myant et al, 2013; Novellasdemunt et al, 2015; Rudy et al, 2016; Pohl et al, 2017; Kartha et al, 2018; Lee et al, 2019; Reyes et al, 2019). The role of WNT7A in oral squamous cell carcinoma (OSCC) is unclear, and this is the focus of our research
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