# Olfactory receptor OR51B5 suppressed esophageal cancer progression through activates Calcium / N-Ras signaling

## TL;DR

This study shows how a specific olfactory receptor, OR51B5, suppresses esophageal cancer by regulating calcium and N-Ras signaling pathways.

## Contribution

The study identifies OR51B5 as a novel tumor suppressor in esophageal cancer through a new regulatory mechanism involving chromatin modification.

## Key findings

- OR51B5 acts as a key spatial element in suppressing esophageal cancer progression.
- CTCF-EZH2 increases H3K27me3 at the OR51B5 promoter, leading to repressed transcription.
- OR51B5 suppression activates N-Ras, promoting tumor proliferation and metastasis.

## Abstract

The transcriptional regulation of olfactory receptors (ORs) plays a critical role in various biological processes, and has recently been considered a potential therapeutic target for cancer treatment. Esophageal cancer (EC) is a highly invasive neoplasm with dismal prognosis, but the specific roles of ORs in EC remain largely unexplored. Here, we developed a comprehensive workflow to identify potential functional olfactory receptor family 51 subfamily B member 5 (OR51B5) and demonstrated that OR51B5 locus acted as a key spatial element contributing to the progression of esophageal cancer. Moreover, we showed that the CTCF-EZH2 enhanced the trimethylation of lysine 27 of histone H3 (H3K27me3) and increased repressive and closed chromatin state at the OR51B5 promoter region. Subsequently we demonstrated that closed chromatin impaired the entry of RNA polymerase II and inhibited the transcription of OR51B5, thereby causing N-Ras activation and promoting tumor cell proliferation and metastasis. Our study provides an alternative workflow for discovering critical regulatory sites for control tumorigenesis, and reveals a novel OR51B5 triggering mechanism underlying esophageal cancer progression.