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Article

The GNAQ T96S Mutation Affects Cell Signaling and Enhances the Oncogenic Properties of Hepatocellular Carcinoma

1
Department of Medical Life Sciences, Department of Biomedicine & Health Sciences, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea
2
College of Pharmacy and Gachon Institute of Pharmaceutical Sciences, Gachon University, Incheon 21936, Korea
3
Precision Medicine Research Center, Integrated Research Center for Genome Polymorphism, Department of Microbiology, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea
4
Department of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea
5
Department of Life Science, Dongguk University-Seoul, Ilsandong-gu, Goyang-si 10326, Gyeonggi-do, Korea
*
Author to whom correspondence should be addressed.
Academic Editor: Paola Ghiorzo
Int. J. Mol. Sci. 2021, 22(6), 3284; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22063284
Received: 5 March 2021 / Revised: 19 March 2021 / Accepted: 20 March 2021 / Published: 23 March 2021
(This article belongs to the Special Issue Molecular Advances in Cancer Genetics)
Hepatocellular carcinoma (HCC), the most common malignant tumor in the liver, grows and metastasizes rapidly. Despite advances in treatment modalities, the five-year survival rate of HCC remains less than 30%. We sought genetic mutations that may affect the oncogenic properties of HCC, using The Cancer Genome Atlas (TCGA) data analysis. We found that the GNAQ T96S mutation (threonine 96 to serine alteration of the Gαq protein) was present in 12 out of 373 HCC patients (3.2%). To examine the effect of the GNAQ T96S mutation on HCC, we transfected the SK-Hep-1 cell line with the wild-type or the mutant GNAQ T96S expression vector. Transfection with the wild-type GNAQ expression vector enhanced anchorage-independent growth, migration, and the MAPK pathways in the SK-Hep-1 cells compared to control vector transfection. Moreover, cell proliferation, anchorage-independent growth, migration, and the MAPK pathways were further enhanced in the SK-Hep-1 cells transfected with the GNAQ T96S expression vector compared to the wild-type GNAQ-transfected cells. In silico structural analysis shows that the substitution of the GNAQ amino acid threonine 96 with a serine may destabilize the interaction between the regulator of G protein signaling (RGS) protein and GNAQ. This may reduce the inhibitory effect of RGS on GNAQ signaling, enhancing the GNAQ signaling pathway. Single nucleotide polymorphism (SNP) genotyping analysis for Korean HCC patients shows that the GNAQ T96S mutation was found in only one of the 456 patients (0.22%). Our data suggest that the GNAQ T96S hotspot mutation may play an oncogenic role in HCC by potentiating the GNAQ signal transduction pathway. View Full-Text
Keywords: hepatocellular carcinoma; guanine nucleotide-binding protein G(q) subunit alpha; helical domain; somatic mutation; mitogen-activated protein kinase (MAPK) signaling hepatocellular carcinoma; guanine nucleotide-binding protein G(q) subunit alpha; helical domain; somatic mutation; mitogen-activated protein kinase (MAPK) signaling
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MDPI and ACS Style

Choi, E.; Park, S.J.; Lee, G.; Yoon, S.K.; Lee, M.; Lee, S.K. The GNAQ T96S Mutation Affects Cell Signaling and Enhances the Oncogenic Properties of Hepatocellular Carcinoma. Int. J. Mol. Sci. 2021, 22, 3284. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22063284

AMA Style

Choi E, Park SJ, Lee G, Yoon SK, Lee M, Lee SK. The GNAQ T96S Mutation Affects Cell Signaling and Enhances the Oncogenic Properties of Hepatocellular Carcinoma. International Journal of Molecular Sciences. 2021; 22(6):3284. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22063284

Chicago/Turabian Style

Choi, Eugene, Sung J. Park, Gunhee Lee, Seung K. Yoon, Minho Lee, and Suk K. Lee 2021. "The GNAQ T96S Mutation Affects Cell Signaling and Enhances the Oncogenic Properties of Hepatocellular Carcinoma" International Journal of Molecular Sciences 22, no. 6: 3284. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22063284

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