Cargando…
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...
Autores principales: | , , , |
---|---|
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 |
_version_ | 1783344215443374080 |
---|---|
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. |
format | Online Article Text |
id | pubmed-6073545 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT liubin theeffectofgprc5aontheproliferationmigrationabilitychemotherapyresistanceandphosphorylationofgsk3binpancreaticcancer AT yanghai theeffectofgprc5aontheproliferationmigrationabilitychemotherapyresistanceandphosphorylationofgsk3binpancreaticcancer AT pilarskychristian theeffectofgprc5aontheproliferationmigrationabilitychemotherapyresistanceandphosphorylationofgsk3binpancreaticcancer AT webergeorgf theeffectofgprc5aontheproliferationmigrationabilitychemotherapyresistanceandphosphorylationofgsk3binpancreaticcancer AT liubin effectofgprc5aontheproliferationmigrationabilitychemotherapyresistanceandphosphorylationofgsk3binpancreaticcancer AT yanghai effectofgprc5aontheproliferationmigrationabilitychemotherapyresistanceandphosphorylationofgsk3binpancreaticcancer AT pilarskychristian effectofgprc5aontheproliferationmigrationabilitychemotherapyresistanceandphosphorylationofgsk3binpancreaticcancer AT webergeorgf effectofgprc5aontheproliferationmigrationabilitychemotherapyresistanceandphosphorylationofgsk3binpancreaticcancer |