[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-331973-105":59,"doc-detail-331973-en":130},{"code":4,"msg":5,"data":6},0,"success",[7,13,18,23,28,33,38,43,48,51,55],{"id":8,"doc_module":4,"doc_module_name":9,"category_name":10,"show_sort_weight":11,"slug":12},1,"Document","Story & Novel",90,"story-novel",{"id":14,"doc_module":4,"doc_module_name":9,"category_name":15,"show_sort_weight":16,"slug":17},2,"Literature",80,"literature",{"id":19,"doc_module":4,"doc_module_name":9,"category_name":20,"show_sort_weight":21,"slug":22},4,"Exam",70,"exam",{"id":24,"doc_module":4,"doc_module_name":9,"category_name":25,"show_sort_weight":26,"slug":27},5,"Comic",60,"comic",{"id":29,"doc_module":4,"doc_module_name":9,"category_name":30,"show_sort_weight":31,"slug":32},6,"Technology",50,"technology",{"id":34,"doc_module":4,"doc_module_name":9,"category_name":35,"show_sort_weight":36,"slug":37},7,"Healthcare",40,"healthcare",{"id":39,"doc_module":4,"doc_module_name":9,"category_name":40,"show_sort_weight":41,"slug":42},8,"Research & Report",30,"research-report",{"id":44,"doc_module":4,"doc_module_name":9,"category_name":45,"show_sort_weight":46,"slug":47},9,"Religion & Spirituality",20,"religion-spirituality",{"id":46,"doc_module":4,"doc_module_name":9,"category_name":49,"show_sort_weight":46,"slug":50},"World Cup","world-cup",{"id":52,"doc_module":4,"doc_module_name":9,"category_name":53,"show_sort_weight":52,"slug":54},10,"Lifestyle","lifestyle",{"id":56,"doc_module":4,"doc_module_name":9,"category_name":57,"show_sort_weight":24,"slug":58},19,"General","general",{"code":4,"msg":60,"data":61},"ok",{"site_id":62,"language":63,"slug":64,"title":65,"keywords":66,"description":67,"schema_data":68,"social_meta":123,"head_meta":125,"extra_data":127,"updated_unix":129},105,"en","aibzip-creb3l4-promotes-cell-proliferation-via-the-skp2-p27-axis-in-luminal-androgen-receptor-subtype-triple-negative-breast-cancer-abstract","AIbZIP - CREB3L4 Promotes Cell Proliferation via the SKP2-p27 Axis in Luminal Androgen Receptor Subtype Triple-Negative Breast Cancer - Abstract","","Breast cancer causes the highest global incidence and a leading share of cancer deaths, and triple-negative breast cancer (TNBC) has limited actionable targets and poor outcomes. In luminal androgen receptor (LAR) TNBC, androgen-induced basic leucine zipper (AIbZIP/CREB3L4) is strongly upregulated. siRNA depletion of AIbZIP in LAR TNBC cells suppresses proliferation and blocks G1–S transition, with p27 specifically increased. The rise in p27 reflects SKP2-driven proteasomal degradation changes, positioning AIbZIP as a regulator of the p27–SKP2 pathway that may drive LAR TNBC progression.",{"@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/aibzip-creb3l4-promotes-cell-proliferation-via-the-skp2-p27-axis-in-luminal-androgen-receptor-subtype-triple-negative-breast-cancer-abstract/331973/",{"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/aibzip-creb3l4-promotes-cell-proliferation-via-the-skp2-p27-axis-in-luminal-androgen-receptor-subtype-triple-negative-breast-cancer-abstract/331973.png","ImageObject",300,407,{"name":92,"@type":93},"Lucas Martin","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-29","2026-09-21",true,{"@type":102,"interactionType":103,"userInteractionCount":34},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What role does AIbZIP (CREB3L4) play in luminal androgen receptor (LAR) subtype TNBC?","Question",{"text":112,"@type":113},"AIbZIP/CREB3L4 is highly upregulated in the LAR subtype of TNBC and contributes to tumor cell proliferation through regulation of the p27–SKP2 pathway.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How does AIbZIP depletion affect LAR TNBC cell behavior?",{"text":117,"@type":113},"siRNA knockdown of AIbZIP greatly suppresses proliferation and inhibits the G1–S transition in LAR TNBC cell lines.",{"name":119,"@type":110,"acceptedAnswer":120},"How is p27 regulation connected to SKP2 in AIbZIP-depleted cells?",{"text":121,"@type":113},"Protein analyses show p27 is specifically upregulated after AIbZIP depletion, and this change is attributed to protein degradation mediated by the ubiquitin–proteasome system via SKP2 upregulation.","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},331973,1790094149,{"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":34,"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":145},8796095360427,"https://ap-avatar.wpscdn.com/davatar_994ba38a5ba835b3df7d355c54d3ed8d","AIbZIP/CREB3L4 Promotes Cell Proliferation via the SKP2-p27 Axis in Luminal Androgen Receptor Subtype Triple-Negative Breast Cancer  \nTaichi Ito, Atsushi Saito, Yasunao Kamikawa, Nayuta Nakazawa, and Kazunori Imaizumi  \nABSTRACT  \n◥  \nBreast cancer ranks first in incidence and fifth in cancer-related deaths among all types of cancer globally. Among breast cancer, triple-negative breast cancer (TNBC) has few known therapeutic targets anda poor prognosis. Therefore, new therapeutic targetsand strategies against TNBC are required. We found that androgeninduced basic leucine zipper (AIbZIP), also known as cyclic AMP– responsive element-binding protein 3-like protein 4 (CREB3L4), which is encoded by Creb3l4, is highly upregulated in a particular subtype of TNBC, luminal androgen receptor (LAR) subtype. We analyzed the function of AIbZIP through depletion of AIbZIP by siRNA knockdown in LAR subtype TNBC cell lines, MFM223 and MDAMB453 . In AIbZIP-depleted cells, the proliferation ratios of cells were greatly suppressed. Moreover, G1–S transition was inhibited in AIbZIP-depleted cells. We comprehensively analyzed  \nthe expression levels of proteins that regulate G1–S transition and found that p27 was specifically upregulated in AIbZIP-depleted cells. Furthermore, we identified that this p27 downregulation was caused by protein degradation modulated by the ubiquitin– proteasome system via F-box protein S-phase kinase-associated protein 2 (SKP2) upregulation. Our findings demonstrate that AIbZIP is a novel p27–SKP2 pathway-regulating factor and a potential molecule that contributes to LAR subtype TNBC progression.  \nImplications: This research shows a new mechanism for the proliferation of LAR subtype TNBC regulated by AIbZIP, that may provide novel insight into the LAR subtype TNBC progression and the molecular mechanisms involved in cell proliferation.  \nIntroduction  \nBreast cancer ranks first in incidence and fifth highest in cancerrelated deaths among all cancer types globally. Global cancer statistics from 2020 showed that approximately 2.3 million new cases and 685,000 deaths were associated with this disease (1) . Breast cancer is divided into three types defined mainly by receptor and protein expression: luminal breast cancer; HER2-positive breast cancer; and triple-negative breast cancer (TNBC) . Luminal breast cancer is characterized by the expression of either estrogen receptor or progesterone receptor, and inhibitors targeting these are very effective for treatment of this type of breast cancer. HER2-positive breast cancer is characterized by the expression of HER2, and targeted mAbs have greatly improved the prognosis of this cancer type. TNBC is defined by the absence of estrogen receptor, progesterone receptor, and HER2, and exhibits complicated and diverse characteristics compared with luminal breast cancer and HER2-positive breast cancer. Thus, the prognosis of TNBC is poor (2, 3) . Several treatments for TNBC were recently developed, including chemotherapy, pembrolizumab, sacituzumab-govitecan, and targeted therapies such as olaparib for BRCAmutated TNBC. While these treatments are promising, their efficacy is  \nDepartment of Biochemistry, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.  \nCorresponding Authors: Atsushi Saito, Institute of Biomedical & Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima City, Hiroshima 734-8553, Japan. E-mail: [saitoa@hiroshima-u.ac.jp](saitoa@hiroshima-u.ac.jp); and Kazunori Imaizumi, [imaizumi@hiroshima-u.ac.jp](imaizumi@hiroshima-u.ac.jp)  \n[Mol Cancer Res 2024](Mol Cancer Res 2024);[22:373](22:373)–[85](85)  \n[doi:](doi: 10.1158/1541-7786.MCR-23-0629)[ 10.1158/1541-7786.MCR-23-0629](doi: 10.1158/1541-7786.MCR-23-0629)  \nThis open access article is distributed under the Creative Commons AttributionNonCommercial-NoDerivatives 4 . 0 International (CC BY-NC-ND 4 . 0) license.  \n􀀁2024The Authors;Published by the American Association for ","cbCaijHY4GhCCwUq","https://ap.wps.com/l/cbCaijHY4GhCCwUq","pdf",12506083,13,"English","# Abstract\n## Implications\n# Introduction\n## Breast cancer background and TNBC subtypes\n## LAR subtype TNBC and therapeutic challenges","[{\"question\":\"What role does AIbZIP (CREB3L4) play in luminal androgen receptor (LAR) subtype TNBC?\",\"answer\":\"AIbZIP/CREB3L4 is highly upregulated in the LAR subtype of TNBC and contributes to tumor cell proliferation through regulation of the p27–SKP2 pathway.\"},{\"question\":\"How does AIbZIP depletion affect LAR TNBC cell behavior?\",\"answer\":\"siRNA knockdown of AIbZIP greatly suppresses proliferation and inhibits the G1–S transition in LAR TNBC cell lines.\"},{\"question\":\"How is p27 regulation connected to SKP2 in AIbZIP-depleted cells?\",\"answer\":\"Protein analyses show p27 is specifically upregulated after AIbZIP depletion, and this change is attributed to protein degradation mediated by the ubiquitin–proteasome system via SKP2 upregulation.\"}]","AIbZIP - CREB3L4 Promotes Cell Proliferation via the SKP2-p27 Axis in Luminal Androgen Receptor Subtype Triple-Negative Breast Cancer - Abstract | PDF",1789996092,33]