IER3 Facilitates Tumor Progression and Aberrant Glycolysis via Activating wnt/β-Catenin Pathway in Oral Squamous Cell Carcinoma.

Abstract

The function and molecular biological mechanism of immediate early response 3 (IER3) on the tumorigenesis of oral squamous cell carcinoma (OSCC) are aimed to be explored. The effects of IER3 on the proliferation, apoptosis, and mobility of OSCC cells are first assessed utilizing colony formation, EdU assay, flow cytometry, and transwell assay. The effect of IER3 on the glycolytic ability of OSCC cells is validated by detecting the extracellular acidification rate and oxygen consumption rate. Additionally, glycolysis- and wnt/β-catenin signaling-associated protein expressions are examined by western blot. Besides, a mouse tumor xenograft model is established to evaluate the effect of IER3 on tumor progression. IER3 expression is upregulated in OSCC cells and tissues. IER3 enhanced tumor cells' malignant behaviors and also promoted the glycolysis of OSCC cells. Moreover, IER3 is verified to promote the activation of wnt/β-catenin signaling in OSCC. Besides, rescue experiments further proved that IER3 knockdown can inhibit the malignant biological behavior of OSCC cells through inactivating wnt/β-catenin signaling. In vivo, the downregulation of IER3 is also demonstrated to suppress OSCC progression by inactivating wnt/β-catenin signaling. IER3 facilitated tumor progression and aberrant glycolysis via activating wnt/β-catenin pathway in OSCC.