Research Paper Volume 12, Issue 12 pp 11794—11811
GALNT6 promotes breast cancer metastasis by increasing mucin-type O-glycosylation of α2M
- 1 Department of Medical Oncology, The First Hospital of China Medical University, Shenyang 110001, China
- 2 Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, The First Hospital of China Medical University, Shenyang 110001, China
- 3 Department of Internal Medicine, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Shenyang 110042, China
Received: July 16, 2019 Accepted: May 14, 2020 Published: June 18, 2020https://doi.org/10.18632/aging.103349
How to Cite
Copyright © 2020 Liu et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Breast cancer is the most lethal malignancy in women. N-acetylgalactosaminyltransferase 6 (GALNT6) is an enzyme which mediates the initial step of mucin-type O-glycosylation, and has been reported to be involved in mammary carcinogenesis. However, the molecular mechanism of GALNT6 in breast cancer metastasis has not been fully explored. In this study, based on online database analyses and tissue microarrays, the overall survival (OS) of breast cancer patients with high expression of GALNT6 was found to be shorter than those with low expression of GALNT6. Also, high GALNT6 expression was positively correlated with advanced pN stage and pTNM stage. GALNT6 was shown to be able to promote the migration and invasion of breast cancer cells, and enhance the level of mucin-type O-glycosylation of substrates in the supernatants of breast cancer cells. Qualitative mucin-type glycosylomics analysis identified α2M as a novel substrate of GALNT6. Further investigation showed that GALNT6 increased O-glycosylation of α2M, and the following activation of the downstream PI3K/Akt signaling pathway was involved in the promotion of migration and invasion of breast cancer cells. This study identified a new substrate of GALNT6 and provides novel understanding of the role of GALNT6 in promoting metastasis and poor prognosis in breast cancer.