GALNT1 Enhances Malignant Phenotype of Gastric Cancer via Modulating CD44 Glycosylation to Activate the Wnt/β-catenin Signaling Pathway

Zhang, Junchang; Wang, Han; Wu, Jing; Yuan, Cheng; Chen, Songyao; Liu, Shuhao; Huo, Mingyu; Zhang, Changhua; He, Yulong

doi:10.7150/ijbs.73431

Theranostics

International Journal of Medical Sciences

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Journal of Cancer

Journal of Genomics

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Int J Biol Sci 2022; 18(16):6068-6083. doi:10.7150/ijbs.73431 This issue Cite

Research Paper

GALNT1 Enhances Malignant Phenotype of Gastric Cancer via Modulating CD44 Glycosylation to Activate the Wnt/β-catenin Signaling Pathway

Junchang Zhang^1,2*, Han Wang^1,2*, Jing Wu¹, Cheng Yuan¹, Songyao Chen^1,2, Shuhao Liu^1,2, Mingyu Huo^1✉, Changhua Zhang^1✉, Yulong He^1,2✉

1. Digestive Disease Center, The Seventh Affiliated Hospital of Sun Yat-Sen University, Shenzhen, Guangdong 518107, P.R. China.
2. Department of Gastrointestinopancreatic Surgery, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong 510080, P.R. China.
*These authors have contributed equally to this work.

Citation:

Zhang J, Wang H, Wu J, Yuan C, Chen S, Liu S, Huo M, Zhang C, He Y. GALNT1 Enhances Malignant Phenotype of Gastric Cancer via Modulating CD44 Glycosylation to Activate the Wnt/β-catenin Signaling Pathway. Int J Biol Sci 2022; 18(16):6068-6083. doi:10.7150/ijbs.73431. https://www.ijbs.com/v18p6068.htm

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Abstract

O-glycosylation is a widespread post-translational modification of proteins. Aberrant O-glycosylation is a hallmark of cancer. Here, we show that the polypeptide N-acetylgalactosamine-transferase 1 (GALNT1) is frequently upregulated in gastric cancer and is correlated with poor survival. Overexpression of GALNT1 promoted, whereas knockdown suppressed proliferation, migration, and invasion of gastric cancer cells in vitro and in vivo. Mechanistically, GALNT1 enhances aberrant initiation of O-glycosylation and results in CD44 glycoproteins modified with abundant Tn antigens, thereby activating the Wnt/β-catenin signaling pathway. Collectively, this study demonstrates that GALNT1 overexpression in gastric cancer promotes the Wnt/β-catenin signaling pathway via abnormal O-glycosylation of CD44 to enhance malignancy, providing a novel strategy for the development of therapeutic reagents against gastric cancer.

Keywords: Gastric cancer, GALNT1, CD44, O-Glycosylation, Wnt/β-catenin signaling pathway

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APA

Zhang, J., Wang, H., Wu, J., Yuan, C., Chen, S., Liu, S., Huo, M., Zhang, C., He, Y. (2022). GALNT1 Enhances Malignant Phenotype of Gastric Cancer via Modulating CD44 Glycosylation to Activate the Wnt/β-catenin Signaling Pathway. International Journal of Biological Sciences, 18(16), 6068-6083. https://doi.org/10.7150/ijbs.73431.

ACS

Zhang, J.; Wang, H.; Wu, J.; Yuan, C.; Chen, S.; Liu, S.; Huo, M.; Zhang, C.; He, Y. GALNT1 Enhances Malignant Phenotype of Gastric Cancer via Modulating CD44 Glycosylation to Activate the Wnt/β-catenin Signaling Pathway. Int. J. Biol. Sci. 2022, 18 (16), 6068-6083. DOI: 10.7150/ijbs.73431.

NLM

CSE

Zhang J, Wang H, Wu J, Yuan C, Chen S, Liu S, Huo M, Zhang C, He Y. 2022. GALNT1 Enhances Malignant Phenotype of Gastric Cancer via Modulating CD44 Glycosylation to Activate the Wnt/β-catenin Signaling Pathway. Int J Biol Sci. 18(16):6068-6083.

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