Truncation of GalNAc-type O-glycans Suppresses CD44-mediated Osteoclastogenesis and Bone Metastasis in Breast Cancer-Reference-Cited by-同舟云学术

Truncation of GalNAc-type O-glycans Suppresses CD44-mediated Osteoclastogenesis and Bone Metastasis in Breast Cancer

Published:2023-04-11 Issue:7 Volume:21 Page:664-674
ISSN:1541-7786
Container-title:Molecular Cancer Research
language:en
Short-container-title:

Author:

Lin Neng-Yu¹^ORCID,Lee Jian-Jr²³^ORCID,Chen Syue-Ting¹⁴^ORCID,Lin Jung-An¹^ORCID,Lin Chia-Hsuan¹^ORCID,Lin Hsuan-Yu¹^ORCID,Su Yong-Han⁵^ORCID,Chen Cheng-Chang⁵⁶^ORCID,Lin Mei-Chun⁷^ORCID,Kuo Ching-Ying⁵⁶^ORCID,Huang Min-Chuan¹^ORCID

Affiliation:

1. 1Graduate Institute of Anatomy and Cell Biology, College of Medicine, National Taiwan University, Taipei, Taiwan.

2. 2Department of Plastic and Reconstructive Surgery, China Medical University Hospital, Taichung, Taiwan.

3. 3School of Medicine, China Medical University, Taichung City, Taiwan.

4. 4Department of Anatomy, Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan.

5. 5Department of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan University, Taipei, Taiwan.

6. 6Department of Laboratory Medicine, National Taiwan University Hospital, Taipei, Taiwan.

7. 7Department of Otolaryngology, National Taiwan University Hospital, Taipei, Taiwan.

Abstract

Abstract The glycoprotein CD44 is a key regulator of malignant behaviors in breast cancer cells. To date, hyaluronic acid (HA)-CD44 signaling pathway has been widely documented in the context of metastatic bone diseases. Core 1 β1,3-galactosyltransferase (C1GALT1) is a critical enzyme responsible for the elongation of O-glycosylation. Aberrant O-glycans is recognized as a hallmark in cancers. However, the effects of C1GALT1 on CD44 signaling and bone metastasis remain unclear. In this study, IHC analysis indicated that C1GALT1 expression positively correlates with CD44 in breast cancer. Silencing C1GALT1 accumulates the Tn antigen on CD44, which decreases CD44 levels and osteoclastogenic signaling. Mutations in the O-glycosites on the stem region of CD44 impair its surface localization as well as suppress cell–HA adhesion and osteoclastogenic effects of breast cancer cells. Furthermore, in vivo experiments demonstrated the inhibitory effect of silencing C1GALT1 on breast cancer bone metastasis and bone loss. In conclusion, our study highlights the importance of O-glycans in promoting CD44-mediated tumorigenic signals and indicates a novel function of C1GALT1 in driving breast cancer bone metastasis. Implications: Truncation of GalNAc-type O-glycans by silencing C1GALT1 suppresses CD44-mediated osteoclastogenesis and bone metastasis in breast cancer. Targeting the O-glycans on CD44 may serve as a potential therapeutic target for blocking cancer bone metastasis.

Funder

n/a

Publisher

American Association for Cancer Research (AACR)

Subject

Cancer Research,Oncology,Molecular Biology

Link

https://aacrjournals.org/mcr/article-pdf/doi/10.1158/1541-7786.MCR-22-0907/3322960/mcr-22-0907.pdf

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