Store-Operated Calcium Channels as Drug Target in Gastroesophageal Cancers.

Yan Chang,Souvik Roy,Zui Pan

doi:10.3389/fphar.2021.668730

Yan Chang, Souvik Roy + Show 1 more

Open Access

https://doi.org/10.3389/fphar.2021.668730

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Abstract

Gastroesophageal cancers, including tumors occurring in esophagus and stomach, usually have poor prognosis and lack effective chemotherapeutic drugs for treatment. The association between dysregulated store-operated calcium entry (SOCE), a key intracellular Ca2+ signaling pathway and gastroesophageal cancers are emerging. This review summarizes the recent advances in understanding the contribution of SOCE-mediated intracellular Ca2+ signaling to gastroesophageal cancers. It assesses the pathophysiological role of each component in SOCE machinery, such as Orais and STIMs in the cancer cell proliferation, migration, and invasion as well as stemness maintenance. Lastly, it discusses efforts towards development of more specific and potent SOCE inhibitors, which may be a new set of chemotherapeutic drugs appearing at the horizon, to provide either targeted therapy or adjuvant treatment to overcome drug resistance for gastroesophageal cancers.

Highlights

Gastroesophageal CancersGastroesophageal (GE) cancers are malignancies that occur in upper gastrointestinal track, including esophageal, gastric and gastroesophageal junction, and are usually presented with poor prognosis (Hsu et al, 2020)
We summarized the recent studies on the role of store-operated calcium entry (SOCE) in Gastroesophageal CancersGastroesophageal (GE) cancers
Since Ca2+ plays a vital role in the epidermal growth factor receptor (EGFR) signaling pathway, SOCE-mediated signaling pathway may crosstalk with EGFR pathway

Summary

Introduction

Gastroesophageal CancersGastroesophageal (GE) cancers are malignancies that occur in upper gastrointestinal track, including esophageal, gastric and gastroesophageal junction, and are usually presented with poor prognosis (Hsu et al, 2020). We intent to discuss an emerging new drug target, known as the store-operated Ca2+ entry (SOCE), which is a key intracellular Ca2+ signaling pathway in GE cancers. Besides Orai and STIM molecules, transient receptor potential canonical (TRPC) family of Ca2+ permeable channels are involved in the SOCE pathway.

Results

Conclusion