caa a22 4500 606235779 CHVBK 20210128101244.0 cr unu---uuuuu 210128e20151201xx s 000 0 eng 10.1007/s11010-015-2542-8 doi (NATIONALLICENCE)springer-10.1007/s11010-015-2542-8 MAPK/ERK signaling pathway-induced hyper-O-GlcNAcylation enhances cancer malignancy [Elektronische Daten] [Xinling Zhang, Leina Ma, Jieqiong Qi, Hui Shan, Wengong Yu, Yuchao Gu] Dysregulated MAPK/ERK signaling is implicated in one-third of human tumors and represents an attractive target for the development of anticancer drugs. Similarly, elevated protein O-GlcNAcylation and O-GlcNAc transferase (OGT) are detected in various cancers and serve as attractive novel cancer-specific therapeutic targets. However, the potential connection between them remains unexplored. Here, a positive correlation was found between the activated MAPK/ERK signaling and hyper-O-GlcNAcylation in various cancer types and inhibition of the MAPK/ERK signaling by 10µM U0126 significantly decreased the expression of OGT and O-GlcNAcylation in H1299, BPH-1 and DU145 cells; then, the pathway analysis of the potential regulators of OGT obtained from the UCSC Genome Browser was done, and ten downstream targets of ERK pathway were uncovered; the following results showed that ELK1, one of the ten targets of ERK pathway, mediated ERK signaling-induced OGT upregulation; finally, the MTT assay and the soft agar assay showed that the inhibition of MAPK/ERK signaling reduced the promotion effect of hyper-O-GlcNAcylation on cancer cell proliferation and anchorage-independent growth. Taken together, our data originally provided evidence for the regulatory mechanism of hyper-O-GlcNAcylation in tumors, which will be helpful for the development of anticancer drugs targeting to hyper-O-GlcNAcylation. This study also provided a new mechanism by which MAPK/ERK signaling-enhanced cancer malignancy. Altogether, the recently discovered oncogenic factor O-GlcNAc was linked to the classical MAPK/ERK signaling which is essential for the maintenance of malignant phenotype of cancers. Springer Science+Business Media New York, 2015 O-GlcNAcylation nationallicence OGT nationallicence Cancer nationallicence Pathway Analysis nationallicence MAPK/ERK nationallicence Zhang Xinling Key Laboratory of Marine Drugs, Chinese Ministry of Education; Key Laboratory of Glycoscience & Glycotechnology of Shandong Province; School of Medicine and Pharmacy, Ocean University of China, 5 Yushan Road, 266003, Qingdao, China aut Ma Leina Key Laboratory of Marine Drugs, Chinese Ministry of Education; Key Laboratory of Glycoscience & Glycotechnology of Shandong Province; School of Medicine and Pharmacy, Ocean University of China, 5 Yushan Road, 266003, Qingdao, China aut Qi Jieqiong Key Laboratory of Marine Drugs, Chinese Ministry of Education; Key Laboratory of Glycoscience & Glycotechnology of Shandong Province; School of Medicine and Pharmacy, Ocean University of China, 5 Yushan Road, 266003, Qingdao, China aut Shan Hui Key Laboratory of Marine Drugs, Chinese Ministry of Education; Key Laboratory of Glycoscience & Glycotechnology of Shandong Province; School of Medicine and Pharmacy, Ocean University of China, 5 Yushan Road, 266003, Qingdao, China aut Yu Wengong Key Laboratory of Marine Drugs, Chinese Ministry of Education; Key Laboratory of Glycoscience & Glycotechnology of Shandong Province; School of Medicine and Pharmacy, Ocean University of China, 5 Yushan Road, 266003, Qingdao, China aut Gu Yuchao Key Laboratory of Marine Drugs, Chinese Ministry of Education; Key Laboratory of Glycoscience & Glycotechnology of Shandong Province; School of Medicine and Pharmacy, Ocean University of China, 5 Yushan Road, 266003, Qingdao, China aut Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 410/1-2(2015-12-01), 101-110 0300-8177 410:1-2<101 2015 410 11010 https://doi.org/10.1007/s11010-015-2542-8 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s11010-015-2542-8 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Zhang Xinling Key Laboratory of Marine Drugs, Chinese Ministry of Education; Key Laboratory of Glycoscience & Glycotechnology of Shandong Province; School of Medicine and Pharmacy, Ocean University of China, 5 Yushan Road, 266003, Qingdao, China aut NATIONALLICENCE 700 1- Ma Leina Key Laboratory of Marine Drugs, Chinese Ministry of Education; Key Laboratory of Glycoscience & Glycotechnology of Shandong Province; School of Medicine and Pharmacy, Ocean University of China, 5 Yushan Road, 266003, Qingdao, China aut NATIONALLICENCE 700 1- Qi Jieqiong Key Laboratory of Marine Drugs, Chinese Ministry of Education; Key Laboratory of Glycoscience & Glycotechnology of Shandong Province; School of Medicine and Pharmacy, Ocean University of China, 5 Yushan Road, 266003, Qingdao, China aut NATIONALLICENCE 700 1- Shan Hui Key Laboratory of Marine Drugs, Chinese Ministry of Education; Key Laboratory of Glycoscience & Glycotechnology of Shandong Province; School of Medicine and Pharmacy, Ocean University of China, 5 Yushan Road, 266003, Qingdao, China aut NATIONALLICENCE 700 1- Yu Wengong Key Laboratory of Marine Drugs, Chinese Ministry of Education; Key Laboratory of Glycoscience & Glycotechnology of Shandong Province; School of Medicine and Pharmacy, Ocean University of China, 5 Yushan Road, 266003, Qingdao, China aut NATIONALLICENCE 700 1- Gu Yuchao Key Laboratory of Marine Drugs, Chinese Ministry of Education; Key Laboratory of Glycoscience & Glycotechnology of Shandong Province; School of Medicine and Pharmacy, Ocean University of China, 5 Yushan Road, 266003, Qingdao, China aut NATIONALLICENCE 773 0- Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 410/1-2(2015-12-01), 101-110 0300-8177 410:1-2<101 2015 410 11010