Next Article in Journal
Programmed Death-Ligand 1 as a Regulator of Tumor Progression and Metastasis
Next Article in Special Issue
Mechanism of Anticancer Action of Novel Imidazole Platinum(II) Complex Conjugated with G2 PAMAM-OH Dendrimer in Breast Cancer Cells
Previous Article in Journal
Retinal Pigment Epithelium Remodeling in Mouse Models of Retinitis Pigmentosa
Previous Article in Special Issue
Potential Antitumor Effects of 6-Gingerol in p53-Dependent Mitochondrial Apoptosis and Inhibition of Tumor Sphere Formation in Breast Cancer Cells
Article

MAT2A Localization and Its Independently Prognostic Relevance in Breast Cancer Patients

by 1,2,3,4,†, 5,6,7,†, 8,†, 6,9,†, 10 and 9,11,*
1
School of Medicine, College of Medicine, Fu Jen Catholic University, New Taipei 242, Taiwan
2
Department of Pathology, Show Chwan Memorial Hospital, Changhua 500, Taiwan
3
Department of Health Food, College of Health, Chung Chou University of Science and Technology, Changhua 510, Taiwan
4
National Institute of Cancer Research, National Health Research Institute, Tainan 704, Taiwan
5
Department of Biology, National Changhua University of Education, Changhua 500, Taiwan
6
Research Assistant Center, Show Chwan Memorial Hospital, Changhua 500, Taiwan
7
Department of Medical Research, Chang Bing Show Chwan Memorial Hospital, Lukang Town, Changhua County 505, Taiwan
8
Department of General Surgery, Show Chwan Memorial Hospital, Changhua 500, Taiwan
9
Department of Food Science and Biotechnology, National Chung Hsing University, Taichung 40402, Taiwan
10
Biomedical Science Laboratory, Department of Nutrition, China Medical University, Taichung 40402, Taiwan
11
Innovation and Development Center of Sustainable Agriculture (IDCSA), National Chung Hsing University, Taichung 40402, Taiwan
*
Author to whom correspondence should be addressed.
These authors contributed equally as first authors of the study.
Academic Editor: Antonella Zannetti
Int. J. Mol. Sci. 2021, 22(10), 5382; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22105382
Received: 11 March 2021 / Revised: 2 May 2021 / Accepted: 13 May 2021 / Published: 20 May 2021
(1) Background: methionine cycle is not only essential for cancer cell proliferation but is also critical for metabolic reprogramming, a cancer hallmark. Hepatic and extrahepatic tissues methionine adenosyltransferases (MATs) are products of two genes, MAT1A and MAT2A that catalyze the formation of S-adenosylmethionine (SAM), the principal biological methyl donor. Glycine N-methyltransferase (GNMT) further utilizes SAM for sarcosine formation, thus it regulates the ratio of SAM:S-adenosylhomocysteine (SAH). (2) Methods: by analyzing the TCGA/GTEx datasets available within GEPIA2, we discovered that breast cancer patients with higher MAT2A had worse survival rate (p = 0.0057). Protein expression pattern of MAT1AA, MAT2A and GNMT were investigated in the tissue microarray in our own cohort (n = 252) by immunohistochemistry. MAT2A C/N expression ratio and cell invasion activity were further investigated in a panel of breast cancer cell lines. (3) Results: GNMT and MAT1A were detected in the cytoplasm, whereas MAT2A showed both cytoplasmic and nuclear immunoreactivity. Neither GNMT nor MAT1A protein expression was associated with patient survival rate in our cohort. Kaplan–Meier survival curves showed that a higher cytoplasmic/nuclear (C/N) MAT2A protein expression ratio correlated with poor overall survival (5 year survival rate: 93.7% vs. 83.3%, C/N ratio ≥ 1.0 vs. C/N ratio < 1.0, log-rank p = 0.004). Accordingly, a MAT2A C/N expression ratio ≥ 1.0 was determined as an independent risk factor by Cox regression analysis (hazard ratio = 2.771, p = 0.018, n = 252). In vitro studies found that breast cancer cell lines with a higher MAT2A C/N ratio were more invasive. (4) Conclusions: the subcellular localization of MAT2A may affect its functions, and elevated MAT2A C/N ratio in breast cancer cells is associated with increased invasiveness. MAT2A C/N expression ratio determined by IHC staining could serve as a novel independent prognostic marker for breast cancer. View Full-Text
Keywords: breast cancer; GNMT; MAT1A; MAT2A; subcellular localization; prognosis breast cancer; GNMT; MAT1A; MAT2A; subcellular localization; prognosis
Show Figures

Figure 1

MDPI and ACS Style

Chu, P.-Y.; Wu, H.-J.; Wang, S.-M.; Chen, P.-M.; Tang, F.-Y.; Chiang, E.-P.I. MAT2A Localization and Its Independently Prognostic Relevance in Breast Cancer Patients. Int. J. Mol. Sci. 2021, 22, 5382. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22105382

AMA Style

Chu P-Y, Wu H-J, Wang S-M, Chen P-M, Tang F-Y, Chiang E-PI. MAT2A Localization and Its Independently Prognostic Relevance in Breast Cancer Patients. International Journal of Molecular Sciences. 2021; 22(10):5382. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22105382

Chicago/Turabian Style

Chu, Pei-Yi, Hsing-Ju Wu, Shin-Mae Wang, Po-Ming Chen, Feng-Yao Tang, and En-Pei I. Chiang 2021. "MAT2A Localization and Its Independently Prognostic Relevance in Breast Cancer Patients" International Journal of Molecular Sciences 22, no. 10: 5382. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22105382

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop