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

被引:33
作者
Liu, Bin [1 ]
Yang, Hai [1 ]
Pilarsky, Christian [1 ]
Weber, Georg F. [1 ]
机构
[1] Univ Klinikum Erlangen, Dept Surg, D-91054 Erlangen, Germany
关键词
pancreatic cancer; GPRC5a; CRISPR/Cas9; system; GSK-3; beta; GLYCOGEN-SYNTHASE KINASE-3; GENE-EXPRESSION; SURVIVAL; IDENTIFICATION; STATISTICS; MICRORNAS;
D O I
10.3390/ijms19071870
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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-3 beta (Glycogen synthase kinase-3 beta) 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.
引用
收藏
页数:14
相关论文
共 44 条
  • [1] Badea L, 2008, HEPATO-GASTROENTEROL, V55, P2016
  • [2] S100P is a metastasis-associated gene that facilitates transendothelial migration of pancreatic cancer cells
    Barry, Sayka
    Chelala, Claude
    Lines, Kate
    Sunamura, Makoto
    Wang, Amu
    Marelli-Berg, Federica M.
    Brennan, Caroline
    Lemoine, Nicholas R.
    Crnogorac-Jurcevic, Tatjana
    [J]. CLINICAL & EXPERIMENTAL METASTASIS, 2013, 30 (03) : 251 - 264
  • [3] Glycogen synthase kinase-3 (GSK3): Regulation, actions, and diseases
    Beurel, Eleonore
    Grieco, Steven F.
    Jope, Richard S.
    [J]. PHARMACOLOGY & THERAPEUTICS, 2015, 148 : 114 - 131
  • [4] Gemcitabine resistance in pancreatic ductal adenocarcinoma
    Binenbaum, Yoav
    Na'ara, Shorook
    Gil, Ziv
    [J]. DRUG RESISTANCE UPDATES, 2015, 23 : 55 - 68
  • [5] UALCAN: A Portal for Facilitating Tumor Subgroup Gene Expression and Survival Analyses
    Chandrashekar, Darshan S.
    Bashel, Bhuwan
    Balasubramanya, Sai Akshaya Hodigere
    Creighton, Chad J.
    Ponce-Rodriguez, Israel
    Chakravarthi, Balabhadrapatruni V. S. K.
    Varambally, Sooryanarayana
    [J]. NEOPLASIA, 2017, 19 (08): : 649 - 658
  • [6] Cancer Statistics in China, 2015
    Chen, Wanqing
    Zheng, Rongshou
    Baade, Peter D.
    Zhang, Siwei
    Zeng, Hongmei
    Bray, Freddie
    Jemal, Ahmedin
    Yu, Xue Qin
    He, Jie
    [J]. CA-A CANCER JOURNAL FOR CLINICIANS, 2016, 66 (02) : 115 - 132
  • [7] Algorithmic Tools for Mining High-Dimensional Cytometry Data
    Chester, Cariad
    Maecker, Holden T.
    [J]. JOURNAL OF IMMUNOLOGY, 2015, 195 (03) : 773 - 779
  • [8] Cancer survival in Europe 1999-2007 by country and age: results of EUROCARE-5-a population-based study
    De Angelis, Roberta
    Sant, Milena
    Coleman, Michel P.
    Francisci, Silvia
    Baili, Paolo
    Pierannunzio, Daniela
    Trama, Annalisa
    Visser, Otto
    Brenner, Hermann
    Ardanaz, Eva
    Bielska-Lasota, Magdalena
    Engholm, Gerda
    Nennecke, Alice
    Siesling, Sabine
    Berrino, Franco
    Capocaccia, Riccardo
    [J]. LANCET ONCOLOGY, 2014, 15 (01) : 23 - 34
  • [9] Glycogen synthase kinase-3 is a pivotal mediator of cancer invasion and resistance to therapy
    Domoto, Takahiro
    Pyko, Ilya V.
    Furuta, Takuya
    Miyashita, Katsuyoshi
    Uehara, Masahiro
    Shimasaki, Takeo
    Nakada, Mitsutoshi
    Minamoto, Toshinari
    [J]. CANCER SCIENCE, 2016, 107 (10): : 1363 - 1372
  • [10] Integrative Survival-Based Molecular Profiling of Human Pancreatic Cancer
    Donahue, Timothy R.
    Tran, Linh M.
    Hill, Reginald
    Li, Yunfeng
    Kovochich, Anne
    Calvopina, Joseph H.
    Patel, Sanjeet G.
    Wu, Nanping
    Hindoyan, Antreas
    Farrell, James J.
    Li, Xinmin
    Dawson, David W.
    Wu, Hong
    [J]. CLINICAL CANCER RESEARCH, 2012, 18 (05) : 1352 - 1363