Journal Article

Calcium-sensing Receptor, a Potential Biomarker Revealed by Large-scale Public Databases and Experimental Verification in Metastatic Breast Cancer

Lin, Xin, Xu, Huimin, Sun, Yihua, Xie, Wanlin, Zeng, Jingya, Cheng, Yangyang

2024

Overview

Introduction Breast cancer (BC) is a common cancer characterized by a high molecular heterogeneity. Therefore, understanding its biological properties and developing effective treatments for patients with different molecular features is imperative. Calcium-sensing receptor (CaSR) has been implicated in several regulatory functions in various types of human cancers. However, its underlying pathological mechanism in BC progression remains elusive. Methods We utilized The Cancer Genome Atlas and Gene Expression Omnibus databases to explore the function of CaSR in the metastasis of BC. Gene ontology analysis, Kyoto Encyclopedia of Genes and Genomes analysis, and Gene Set Enrichment Analysis of biological processes and cell signaling pathways revealed that CaSR could be activated or inhibited. Importantly, quantitative reverse transcriptase-polymerase chain reaction and western blotting were used to verify the gene expression of the CaSR. Wound healing and transwell assays were conducted to assess the effect of CaSR on the migration of BC cells. Results We demonstrated that CaSR expression in metastatic BC was higher than that in non-metastatic BC. It is the first time that database information has been used to reveal the biological process and molecular mechanism of CaSR in BC. Moreover, the CaSR expression in normal breast epithelial cells was notably less compared to that in BC cells. The activation of CaSR by Cinacalcet (a CaSR agonist) significantly enhanced the migration of BC cells, whereas NPS-2143 (a CaSR antagonist) treatment dramatically inhibited these effects. Conclusion and future perspective Bioinformatics techniques and experiments demonstrated the involvement of CaSR in BC metastasis. Our findings shed new light on the receptor therapy and molecular pathogenesis of BC, and emphasize the crucial function of CaSR, facilitating the metastasis of BC.

• Publisher: SAGE Publications,Sage Publications Ltd,SAGE Publishing
• Subject: Bioinformatics / Biomarkers, Tumor - genetics / Biomarkers, Tumor - metabolism / Breast cancer / Breast Neoplasms - genetics / Breast Neoplasms - metabolism / Breast Neoplasms - pathology / Calcium-sensing receptors / Cancer therapies / Cell activation / Cell Line, Tumor / Cell migration / Cell Movement - genetics / Cell signaling / Computational Biology - methods / Databases, Genetic / Epithelial cells / Female / Gene expression / Gene Expression Profiling / Gene Expression Regulation, Neoplastic / Gene Ontology / Gene set enrichment analysis / Genomic analysis / Humans / Information processing / Metastases / Metastasis / Molecular modelling / Neoplasm Metastasis / Receptors, Calcium-Sensing - genetics / Receptors, Calcium-Sensing - metabolism / RNA-directed DNA polymerase / Signal Transduction / Western blotting / Wound healing