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The Effect of GPRC5a on the Proliferation, Migration Ability, Chemotherapy Resistance, and Phosphorylation of GSK-3β in Pancreatic Cancer

Pancreatic cancer (PaCa) is the fourth leading cause of cancer-related death, and personalized targeted cancer therapy is becoming a promising treatment strategy for PaCa. The central approach of targeted therapy is to find a targetable key and an effective targeting method. In this study, the impor...

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Autores principales: Liu, Bin, Yang, Hai, Pilarsky, Christian, Weber, Georg F.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6073545/
https://www.ncbi.nlm.nih.gov/pubmed/29949874
http://dx.doi.org/10.3390/ijms19071870
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author Liu, Bin
Yang, Hai
Pilarsky, Christian
Weber, Georg F.
author_facet Liu, Bin
Yang, Hai
Pilarsky, Christian
Weber, Georg F.
author_sort Liu, Bin
collection PubMed
description Pancreatic cancer (PaCa) is the fourth leading cause of cancer-related death, and personalized targeted cancer therapy is becoming a promising treatment strategy for PaCa. The central approach of targeted therapy is to find a targetable key and an effective targeting method. In this study, the importance of GPRC5a (the G-protein-coupled receptor family C, member 5, group A) was identified using data mining methods based on published datasets. After analysis of the basic expression of GPRC5a in normal pancreas tissue and various PaCa cell lines, gene editing of GPRC5a in the human PaCa cell line MIA PaCa-2 and the mouse PaCa cell line TB32047 was performed using CRISPR/Cas9 (Clustered Regularly Interspaced Short Palindromic Repeats/CRISPR-associated proteins 9) to investigate the influence of GPRC5a on the proliferation and migration of PaCa cells as well as its effects on chemotherapy drug resistance. The results showed that GPRC5a was upregulated in PaCa tissues and various PaCa cell lines. Knockout of GPRC5a reduced the proliferation and migration ability of PaCa cell lines and suppressed the chemotherapy drug resistance of gemcitabine, oxaliplatin, and fluorouracil in PaCa cells. The phosphorylation of GSK-3β (Glycogen synthase kinase-3β) was found to be upregulated in the MIA PaCa-2 and TB32047 cells after GPRC5a knockout. In conclusion, GPRC5a was upregulated in PaCa leading to an enhanced drug resistance in PaCa cells. These results provide for the first time a theoretical basis for the development of an improved PaCa targeted therapy.
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spelling pubmed-60735452018-08-13 The Effect of GPRC5a on the Proliferation, Migration Ability, Chemotherapy Resistance, and Phosphorylation of GSK-3β in Pancreatic Cancer Liu, Bin Yang, Hai Pilarsky, Christian Weber, Georg F. Int J Mol Sci Article Pancreatic cancer (PaCa) is the fourth leading cause of cancer-related death, and personalized targeted cancer therapy is becoming a promising treatment strategy for PaCa. The central approach of targeted therapy is to find a targetable key and an effective targeting method. In this study, the importance of GPRC5a (the G-protein-coupled receptor family C, member 5, group A) was identified using data mining methods based on published datasets. After analysis of the basic expression of GPRC5a in normal pancreas tissue and various PaCa cell lines, gene editing of GPRC5a in the human PaCa cell line MIA PaCa-2 and the mouse PaCa cell line TB32047 was performed using CRISPR/Cas9 (Clustered Regularly Interspaced Short Palindromic Repeats/CRISPR-associated proteins 9) to investigate the influence of GPRC5a on the proliferation and migration of PaCa cells as well as its effects on chemotherapy drug resistance. The results showed that GPRC5a was upregulated in PaCa tissues and various PaCa cell lines. Knockout of GPRC5a reduced the proliferation and migration ability of PaCa cell lines and suppressed the chemotherapy drug resistance of gemcitabine, oxaliplatin, and fluorouracil in PaCa cells. The phosphorylation of GSK-3β (Glycogen synthase kinase-3β) was found to be upregulated in the MIA PaCa-2 and TB32047 cells after GPRC5a knockout. In conclusion, GPRC5a was upregulated in PaCa leading to an enhanced drug resistance in PaCa cells. These results provide for the first time a theoretical basis for the development of an improved PaCa targeted therapy. MDPI 2018-06-26 /pmc/articles/PMC6073545/ /pubmed/29949874 http://dx.doi.org/10.3390/ijms19071870 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Liu, Bin
Yang, Hai
Pilarsky, Christian
Weber, Georg F.
The Effect of GPRC5a on the Proliferation, Migration Ability, Chemotherapy Resistance, and Phosphorylation of GSK-3β in Pancreatic Cancer
title The Effect of GPRC5a on the Proliferation, Migration Ability, Chemotherapy Resistance, and Phosphorylation of GSK-3β in Pancreatic Cancer
title_full The Effect of GPRC5a on the Proliferation, Migration Ability, Chemotherapy Resistance, and Phosphorylation of GSK-3β in Pancreatic Cancer
title_fullStr The Effect of GPRC5a on the Proliferation, Migration Ability, Chemotherapy Resistance, and Phosphorylation of GSK-3β in Pancreatic Cancer
title_full_unstemmed The Effect of GPRC5a on the Proliferation, Migration Ability, Chemotherapy Resistance, and Phosphorylation of GSK-3β in Pancreatic Cancer
title_short The Effect of GPRC5a on the Proliferation, Migration Ability, Chemotherapy Resistance, and Phosphorylation of GSK-3β in Pancreatic Cancer
title_sort effect of gprc5a on the proliferation, migration ability, chemotherapy resistance, and phosphorylation of gsk-3β in pancreatic cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6073545/
https://www.ncbi.nlm.nih.gov/pubmed/29949874
http://dx.doi.org/10.3390/ijms19071870
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