BTC as a Novel Biomarker Contributing to EMT via the PI3K-AKT Pathway in OSCC

Abstract

Purpose: Oral squamous cell carcinoma (OSCC) is one of the most common malignant tumors of the head and neck, while metastasis is the main cause of OSCC-related death. There is an urgent need to explore novel prognostic biomarkers and identify biological targets related to metastasis in OSCC treatment.Methods: Analysis of differential expression was performed using datasets in The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). Immunohistochemistry (IHC) was conducted to assess the expression of betacellulin (BTC) in OSCC. SCC4 and CAL27 cells were used for in vitro experiments, in which CCK-8, transwell assays, and wounding healing assays were performed to verify the biological functions of BTC. The role of BTC in EMT was analyzed by EMT score and Western blot.Results: Through the analysis of the mRNA expression profile data from TCGA database in OSCC, we found that only low expression of BTC was significantly correlated with a poor prognosis in OSCC patients. The results of IHC assays and TCGA databases showed that the expression level of BTC was related to the tumor stage, histological grade, and metastasis status. In vitro analysis showed that overexpression of BTC significantly suppressed the proliferation and migration of OSCC cells. Furthermore, we confirmed that BTC could affect EMT through the PI3K-AKT signaling pathway.Conclusion: The overexpression of BTC suppresses the proliferation, migration, and EMT of OSCC cells via the PI3K-AKT pathways, leading to a better prognosis in OSCC. BTC may be used as a novel molecular marker to assess the prognosis of OSCC patients.

ZNF692 promotes cell proliferation, invasion and migration of human prostate cancer cells by targeting the EMT signaling pathway

“…Secondly, ZNF692 may also affect multiple signaling pathways associated with EMT. For example, ZNF692 may be involved in activating pathways such as Wnt/ beta-catenin, Notch, or Hedgehog, which play a key role in the EMT process and self-renewal of cancer stem cells [ 19 – 21 ]. By affecting these signaling pathways, ZNF692 may not only promote EMT, but also the maintenance and proliferation of cancer stem cells, which is critical for tumor persistence and resistance to treatment.…”