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This study identifies N-linked glycosylation as a critical functional post-translational modification for KIAA1324 activity. Disrupting N-glycosylation abolishes suppression of cancer-cell proliferation, migration, apoptosis, and tumor regression. Inhibition of fucosylation further blocks KIAA1324-driven growth inhibition and apoptosis. Mechanistically, N-linked glycosylation stabilizes KIAA1324, modulates apoptosis and cell-cycle arrest pathways by RNA sequencing, and alters localization and GRP78–caspase 7 interactions in non-glycosylated mutants.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/n-linked-glycosylation-is-essential-for-anti-tumor-activities-of-kiaa1324-in-gastric-cancer/378136/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/n-linked-glycosylation-is-essential-for-anti-tumor-activities-of-kiaa1324-in-gastric-cancer/378136.png","ImageObject",300,407,{"name":92,"@type":93},"วิน","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-29","2026-09-24",true,{"@type":102,"interactionType":103,"userInteractionCount":52},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What is the main finding about KIAA1324 in gastric cancer?","Question",{"text":112,"@type":113},"N-linked glycosylation is essential for KIAA1324’s anti-tumor activity in gastric cancer, supporting inhibition of proliferation, migration, and apoptosis, as well as tumor regression.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How does loss of N-linked glycosylation affect KIAA1324 function?",{"text":117,"@type":113},"Eliminating N-linked glycosylation removes KIAA1324’s ability to suppress cancer-cell proliferation and migration and inhibits apoptosis and tumor regression, with reduced protein stability via rapid proteasomal degradation.",{"name":119,"@type":110,"acceptedAnswer":120},"What role do fucosylation and GRN/RNA-seq analyses play in the study?",{"text":121,"@type":113},"KIAA1324 undergoes fucosylation, and blocking fucosylation suppresses KIAA1324-induced growth inhibition and apoptosis. RNA sequencing and gene regulatory network analyses identify pathways and transcriptional targets related to apoptosis and cell-cycle arrest modulated by glycosylated KIAA1324.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},378136,1790535326,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":52,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":139,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":41},2336475104736,"https://ap-avatar.wpscdn.com/avatar/22000c4c5e0e5b17e70?x-image-process=image/resize,m_fixed,w_180,h_180&k=1786591360781797222","[www.nature.com/cddis](www.nature.com/cddis)  \nARTICLE OPEN   \nN-linked glycosylation is essential for anti-tumor activities of KIAA1324 in gastric cancer  \nRebecca Yun 1,2,11, Eunji Hong 1,3,11, Junil Kim4,11, Bora Park5, Staci Jakyong Kim6, Bona Lee7, Yong Sang Song 2,8, Seong-Jin Kim 1,9, Sujin Park1 ✉ and Jin Muk Kang 10 ✉  \n© The Author(s) 2023  \n\n| | KIAA1324 is a transmembrane protein largely reported as a tumor suppressor and favorable prognosis marker in various cancers, including gastric cancer. In this study, we report the role of N-linked glycosylation in KIAA1324 as a functional post-translational modification (PTM) . Loss of N-linked glycosylation eliminated the potential of KIAA1324 to suppress cancer cell proliferation and migration. Furthermore, we demonstrated that KIAA1324 undergoes fucosylation, a modification of the N-glycan mediated by fucosyltransferase, and inhibition of fucosylation also significantly suppressed KIAA1324-induced cell growth inhibition and apoptosis of gastric cancer cells. In addition, KIAA1324-mediated apoptosis and tumor regression were inhibited by the loss of N-linked glycosylation. RNA sequencing (RNAseq) analysis revealed that genes most relevant to the apoptosis and cell cycle arrest pathways were modulated by KIAA1324 with the N-linked glycosylation, and Gene Regulatory Network (GRN) analysis suggested novel targets of KIAA1324 for anti-tumor effects in the transcription level. The N-linked glycosylation blockade decreased protein stability through rapid proteasomal degradation. The non-glycosylated mutant also showed altered localization and lost apoptotic activity that inhibits the interaction between GRP78 and caspase 7. These data demonstrate that N-linked glycosylation of KIAA1324 is essential for the suppressive role of KIAA1324 protein in gastric cancer progression and indicates that KIAA1324 may have antitumor effects by targeting cancer-related genes with N-linked glycosylation. In conclusion, our study suggests the PTM of KIAA1324 | |\n| --- | --- | --- |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  | including N-linked glycosylation and fucosylation is a necessary factor to consider for cancer prognosis and therapy improvement. |  |\n|  |  |  |\n|  |  |  |\n|  | Cell Death and Disease (2023)14:546; [https://doi.org/10.1038/s41419-023-06083-6](https://doi.org/10.1038/s41419-023-06083-6) |  |\n|  |  |  |\n\nINTRODUCTION  \nAdvanced technology is leading the discovery of novel cancerrelated genes [1], deepening our understanding of cancer and improving therapeutic strategies. Most research on novel genes has been initially approached based on their expression level, but the functions of genes are influenced by many other factors such as interacting partners and post-transcriptional or translational modifications. To predict the action and impact of the genes on cancer precisely, altered modifications of genes or partners are being revealed through continuous research.  \nPost-translational modifications (PTMs) are chemical changes toa protein that alter its properties, conformation, and binding capacity [2] . PTMs control the activity, stability, and localization of proteins, thereby regulating most biological processes including cell growth, migration, and differentiation. Since PTMs are critical for the normal function of proteins, alterations are often correlated with oncogenesis, cancer development, and malignancy [3, 4] .  \nAmong PTMs, glycosylation, the attachment of glycan, is coordinated by the complex effort of nucleotide sugar  \ntransporters, glycosyltransferases, and glycosidases and initiated in the endoplasmic reticulum or Golgi apparatus [5] . Glycans added to and extending away from the surface of proteins contribute to three-dimensional conformation, overall charge, protein function, localization, and stability. N-linked glycosylation (N-glycosylation) occurs at the nitr","cbCairF7injvIi9G","https://ap.wps.com/l/cbCairF7injvIi9G","pdf",4376812,12,"English","# INTRODUCTION\n## Post-translational modifications (PTMs) and cancer\n## Glycosylation and N-glycosylation in tumor biology","[{\"question\":\"What is the main finding about KIAA1324 in gastric cancer?\",\"answer\":\"N-linked glycosylation is essential for KIAA1324’s anti-tumor activity in gastric cancer, supporting inhibition of proliferation, migration, and apoptosis, as well as tumor regression.\"},{\"question\":\"How does loss of N-linked glycosylation affect KIAA1324 function?\",\"answer\":\"Eliminating N-linked glycosylation removes KIAA1324’s ability to suppress cancer-cell proliferation and migration and inhibits apoptosis and tumor regression, with reduced protein stability via rapid proteasomal degradation.\"},{\"question\":\"What role do fucosylation and GRN/RNA-seq analyses play in the study?\",\"answer\":\"KIAA1324 undergoes fucosylation, and blocking fucosylation suppresses KIAA1324-induced growth inhibition and apoptosis. RNA sequencing and gene regulatory network analyses identify pathways and transcriptional targets related to apoptosis and cell-cycle arrest modulated by glycosylated KIAA1324.\"}]","N-linked glycosylation is essential for anti-tumor activities of KIAA1324 in gastric cancer | PDF",1790228628]