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. 2021 Feb;45(2):320-333.
doi: 10.1002/cbin.11488. Epub 2020 Oct 31.

Reduced expression of ppGalNAc-T4 promotes proliferation of human breast cancer cells

Qiong Wu  1 , Xueqin Xie  1 , Keren Zhang  2 , Bachir Niang  3 , Yimin Liu  1 , Cheng Zhang  1 , Tianmiao Huang  1 , Huang Huang  1 , Wenli Li  1 , Jianing Zhang  1 , Yubo Liu  1
Affiliations

Reduced expression of ppGalNAc-T4 promotes proliferation of human breast cancer cells

Qiong Wu et al. Cell Biol Int. 2021 Feb.

Abstract

Breast cancer, one of the most frequently diagnosed and aggressive malignancies, is the major cause of cancer-related death greatly threatening women health. Polypeptide N-acetylgalactosaminyltransferase 4 (ppGalNAc-T4), responsible for the initial step of mucin-type O-glycosylation, has been reported to be implicated in diverse types of human tumors. However, the biological role of ppGalNAc-T4 in breast cancer is still undetermined. In this study, we investigate the effects and mechanism of ppGalNAc-T4 to breast cancer cell proliferation. From analysis of high throughput RNA sequencing datasets of Gene Expression Omnibus and ArrayExpress, a positive correlation between ppGalNAc-T4 and the recurrence-free survival was observed in multigroup of human breast cancer datasets. Moreover, transcriptomes analysis using RNA-sequencing in MCF7 cells revealed that cell cycle-related genes induced the effects of ppGalNAc-T4 on breast cancer cell proliferation. Additionally, investigations showed that ppGalNAc-T4 impaired cell proliferation in MCF-7 and MDA-MB-231 breast cells. Furthermore, our results suggested that the ppGalNAc-T4 knockout activated Notch signaling pathway and enhanced cell proliferation. Collectively, our data indicated that ppGalNAc-T4 affected the proliferation of human breast cancer cells, which appears to be a novel target for understanding the underlying molecular mechanism of breast cancer.

Keywords: Notch signaling pathway; RNA-sequencing; breast cancer cell; cell cycle; cell growth; ppGalNAc-T4.

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