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Addendum published on 27 March 2019, see Int. J. Mol. Sci. 2019, 20(7), 1540.

Open AccessArticle

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

Department of Surgery, Universitätsklinikum Erlangen, Krankenhausstraße 12, 91054 Erlangen, Germany
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Int. J. Mol. Sci. 2018, 19(7), 1870; https://doi.org/10.3390/ijms19071870
Received: 29 April 2018 / Revised: 17 June 2018 / Accepted: 25 June 2018 / Published: 26 June 2018
(This article belongs to the Special Issue Cancer-Driver G Protein-Coupled Receptors as Therapeutic Targets)
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Abstract

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. View Full-Text
Keywords: pancreatic cancer; GPRC5a; CRISPR/Cas9 system; GSK-3β pancreatic cancer; GPRC5a; CRISPR/Cas9 system; GSK-3β
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Liu, B.; Yang, H.; Pilarsky, C.; Weber, G.F. The Effect of GPRC5a on the Proliferation, Migration Ability, Chemotherapy Resistance, and Phosphorylation of GSK-3β in Pancreatic Cancer. Int. J. Mol. Sci. 2018, 19, 1870.

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