WNT7A Promotes EGF-Induced Migration of Oral Squamous Cell Carcinoma Cells by Activating β-Catenin/MMP9-Mediated Signaling

Abstract

Aims and hypothesis: Epidermal growth factor (EGF) has been shown to induce the migration of various cancer cells. However, the underlying signaling mechanisms for EGFinduced 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.Methods: Cell migration was measured by Wound healing assay and Transwell assay. Western blotting was carried out to detect the expression of WNT7A, MMP9, b-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 b-catenin was displayed by immunofluorescence microscopy. Immunohistochemistry was carried out to confirm the relation between WNT7A expression and OSCC progression.Results: The 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 b-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. Conclusions:The data in this paper indicated that WNT7A could be a potential oncogene in OSCC and identified a novel PI3K/AKT/WNT7A/b-catenin/MMP9 signaling for EGF-induced migration of OSCC cells.

The effects of aging on molecular modulators of human embryo implantation

“…Focusing on the rba-YMA biological processes, the negative regulation of apoptosis revealed among others, interactions between endometrial EGFR and embryonic UBB, KRT18, and WNT7A, as well as endometrial SOD2 and embryonic PRDX5 (Figure S4; Table S6). Crosstalk between EGF/EGFR and WNT pathways has been reported, consistent with a role in cell migration (Xie et al, 2020;Liu et al, 2017). Apart from their participation in the negative regulation of apoptosis, EGFR is a potential regulator of KRT18 that could also affect cell migration and invasion (Ruan et al, 2011;De Luca et al, 2014;Zhang et al, 2019).…”

Wnt/β-Catenin Signaling in Oral Carcinogenesis

“…On the other hand, Wnt7b has also been found overexpressed in OSCC, and it accounts for the activation of Wnt/β-catenin and tumor cell proliferation and invasion in vitro [ 110 ]. Finally, Wnt7a has been proposed as a promoter of OSCC progression by increasing the MMP-9 expression in a β-catenin-dependent manner [ 111 ]. Collectively, these evidences support the notion that Wnt ligands are relevant players in oral cancer progression.…”

Surfactin from Bacillus subtilis attenuates ambient air particulate matter-promoted human oral cancer cells metastatic potential

“…Moreover, MMP-9 can mediate extracellular matrix (ECM) remodeling by cleaving many ECM proteins. MMP-2 or MMP-9 has been shown to play an important role in regulating metastasis including oral cancer [5,7]. PM2.5 also has been shown to induce MMP-2 and MMP-9 expression in keratinocytes [6].…”

“…Cancer cell migration/invasion is the most important cause of cancer mortality [5]. Surfactin has been shown to possess some properties including anti-cancer, anti-bacterial, and anti-viral activities [11].…”

“…The most common malignant tumor in the oral cavity is oral squamous cell carcinoma (OSCC). Moreover, cancer cell migration/invasion is the most important cause of cancer mortality 5 . Matrix metalloproteinases (MMPs) belong to a family of zinc-dependent endopeptidases 6 .…”