Roles of Nuclear Receptors in Esophageal Cancer

Abstract

Background: Esophageal cancer (EC), including esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC), is a highly prevalent malignancy that occurs predominantly in the Asian region and is related to ethnicity, genetics, diet, and lifestyle. The nuclear receptor (NR) superfamily consists of 48 members of the human body. It is a collection of a large class of transcription factors, including Peroxisome proliferator-activated receptors (PPARs), Farnesol X receptor (FXR), Vitamin D receptor (VDR), Retinoic acid receptor (RAR), Pregnane X receptor (PXR), Androgen receptor (AR) and so on. Several NRs have been detected as oncogenes or tumor suppressors in EC progression. Objectives: NRs are associated with the progression of many cancers, including EC. Some NRs, such as PPARs and FXR, play an important role in EC. Studying the molecular mechanism of NRs in EC is helpful for further understanding the development of EC. Preclinical research and development of small molecule compound drugs targeting NRs have provided new ideas for the potential targeted therapy of EC. Method: This review summarizes the studies on NRs in EC in recent years, mainly including in vitro cell experiments and in vivo animal experiments. Results: NRs influence EC progress in a variety of ways. They mainly affect the proliferation, migration and drug resistance of EC cells by affecting key cancer cell signaling pathways. Activation or inhibition of NRs inhibits or promotes EC progression, depending on EC types and tumor stages. Preclinical studies mainly focus on the development of small molecule drugs for targeting NRs (such as PPARγ agonists, PPARδ inhibitors, and FXR agonists), and agonists or inhibitors of NRs will become a potential therapeutic regimen for EC. Conclusion: The studies on the roles of NRs in EC have provided a theoretical basis for us to further understand the pathogenesis of EC and develop potential therapeutic drugs targeting NRs for the treatment of different diseasesConclusion: The studies on the roles of NRs in EC have provided a theoretical basis for us to further understand the pathogenesis of EC and develop potential therapeutic drugs targeting NRs for the treatment of different diseases

Blocking SLC7A11 attenuates the proliferation of esophageal squamous cell carcinoma cells

“…Esophageal cancer (EC) is one of the most common malignant tumors and ranks eighth in the world (Han et al 2023 ). EC consists of two histological types: esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC) (Deng et al 2023 ), and more than 90% of all EC patients are ESCC, the main subtype in China (Yang et al 2020 ). Although the therapeutic methods for ESCC have been advanced, however, the prognosis is still entirely unfavorable with a 5-year survival rate of just 25% (Shu et al 2022 ).…”