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IHC shows C1GALT1 expression positively correlates with CD44, while silencing C1GALT1 accumulates the Tn antigen, reduces CD44 and osteoclastogenic signaling, and disrupts stem-region localization and HA adhesion. In vivo, C1GALT1 silencing inhibits bone metastasis and bone loss, supporting a therapeutic O-glycans targeting strategy.",{"@graph":14,"@context":73},[15,34,56],{"@type":16,"itemListElement":17},"BreadcrumbList",[18,23,27,31],{"item":19,"name":20,"@type":21,"position":22},"https://docshare.wps.com","Home","ListItem",1,{"item":24,"name":25,"@type":21,"position":26},"https://docshare.wps.com/document/","Document",2,{"item":28,"name":29,"@type":21,"position":30},"https://docshare.wps.com/document/healthcare/","Healthcare",3,{"item":32,"name":10,"@type":21,"position":33},"https://docshare.wps.com/document/truncation-of-galnac-type-o-glycans-suppresses-cd44-mediated-osteoclastogenesis-and-bone-metastasis-in-breast-cancer/380148/",4,{"url":32,"name":10,"@type":35,"image":36,"author":41,"headline":10,"publisher":44,"fileFormat":47,"inLanguage":8,"description":12,"dateModified":48,"datePublished":49,"encodingFormat":47,"isAccessibleForFree":50,"interactionStatistic":51},"DigitalDocument",{"url":37,"@type":38,"width":39,"height":40},"https://docshare.wps.com/thumbnails/truncation-of-galnac-type-o-glycans-suppresses-cd44-mediated-osteoclastogenesis-and-bone-metastasis-in-breast-cancer/380148.png","ImageObject",300,407,{"name":42,"@type":43},"\tJames","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-11-02","2026-09-24",true,{"@type":52,"interactionType":53,"userInteractionCount":55},"InteractionCounter",{"@type":54},"ViewAction",9,{"@type":57,"mainEntity":58},"FAQPage",[59,65,69],{"name":60,"@type":61,"acceptedAnswer":62},"What role does CD44 play in breast cancer bone metastasis?","Question",{"text":63,"@type":64},"CD44 acts as a key regulator of malignant behaviors in breast cancer cells and participates in HA-mediated signaling that drives osteoclastogenesis and bone homeostasis disruption.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"How does silencing C1GALT1 affect CD44 and osteoclastogenic signaling?",{"text":68,"@type":64},"Silencing C1GALT1 causes Tn antigen accumulation on CD44, which decreases CD44 levels and reduces osteoclastogenic signaling.",{"name":70,"@type":61,"acceptedAnswer":71},"What evidence supports C1GALT1 as a driver of bone metastasis in vivo?",{"text":72,"@type":64},"In vivo experiments show that silencing C1GALT1 inhibits breast cancer bone metastasis and bone 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\nNeng-Yu Lin1, Jian-Jr Lee2,3, Syue-Ting Chen1,4, Jung-An Lin1, Chia-Hsuan Lin1, Hsuan-Yu Lin1, Yong-Han Su5, Cheng-Chang Chen5,6, Mei-Chun Lin7, Ching-Ying Kuo5,6, and Min-Chuan Huang1  \n◥  \nThe 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 b1,3-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 Oglycosites 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  \nnovel function of C1GALT1 in driving breast cancer bone metastasis.  \nImplications: 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.  \nIntroduction  \nBone metastases frequently occur in almost all tumors, especially in 65% to 75% of patients with breast cancer. This high incidence rate has become the leading cause of cancer-related deaths worldwide(1). Bone metastatic breast cancer is mainly duetoosteolytic bone destruction and systemic bone loss by triggering osteoclastogenesis(2) .  \n1Graduate Institute of Anatomy and Cell Biology, College of Medicine, National Taiwan University, Taipei, Taiwan. 2Department of Plastic and Reconstructive Surgery, China Medical University Hospital, Taichung, Taiwan. 3School of Medicine, China Medical University, Taichung City, Taiwan. 4Department of Anatomy, Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan. 5Department of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan University, Taipei, Taiwan. 6Department of Laboratory Medicine, National Taiwan University Hospital, Taipei, Taiwan. 7Department of Otolaryngology, National Taiwan University Hospital, Taipei, Taiwan.  \nCorresponding Author: Neng-Yu Lin, Graduate Institute of Anatomy and Cell Biology, College of Medicine, National Taiwan University, Taipei 100, Taiwan. Phone: 8862-2312-3456, ext. 288179; Fax: 8862-2391-5292; E-mail: [nylin@ntu.edu.tw](nylin@ntu.edu.tw)  \nMol Cancer Res 2023;21:664–74  \ndoi: 10.1158/1541-7786 . MCR-22-0907  \nThis open access article is distributed under the Creative Commons AttributionNonCommercial-NoDerivatives 4 . 0 International (CC BY-NC-ND 4 . 0) license.  \n􀀂2023The Authors;Published by the American Association for Cancer Research  \nIncreasing evidence suggests that breast cancer bone metastasis is relevant to cancer cell–mediated elevation of activators such as Interleukin-1 b (IL1b), Interleukin 6 (IL6), macrophage colony stimulating factor(M-CSF)receptor activator ofnuclear factor kappa-B ligand (RANKL), and CD44 signaling, which activate osteoclasts and disrupt the homeostatic balance of bone formation and degradation (3–9). Particularly, the serum levels of M-CSF, the essential activator of osteoclastogenesis, were significantly higher in patients with bone metastatic cancer than in ","cbCaiq3tMbB50Ans","https://ap.wps.com/l/cbCaiq3tMbB50Ans","pdf",15880921,11,"English","# Implications\n# Introduction\n## Bone metastasis and osteoclastogenesis\n## O-glycosylation and C1GALT1\n## CD44, HA signaling, and glycosylation","[{\"question\":\"What role does CD44 play in breast cancer bone metastasis?\",\"answer\":\"CD44 acts as a key regulator of malignant behaviors in breast cancer cells and participates in HA-mediated signaling that drives osteoclastogenesis and bone homeostasis disruption.\"},{\"question\":\"How does silencing C1GALT1 affect CD44 and osteoclastogenic signaling?\",\"answer\":\"Silencing C1GALT1 causes Tn antigen accumulation on CD44, which decreases CD44 levels and reduces osteoclastogenic signaling.\"},{\"question\":\"What evidence supports C1GALT1 as a driver of bone metastasis in vivo?\",\"answer\":\"In vivo experiments show that silencing C1GALT1 inhibits breast cancer bone metastasis and bone loss.\"}]","Truncation of GalNAc-type O-glycans Suppresses CD44-mediated Osteoclastogenesis and Bone Metastasis in Breast Cancer | PDF",1790239012,28]