[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-448030-105":59,"doc-detail-448030-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","perp-suppresses-breast-cancer-metastasis-via-the-atf3hspa6-signaling-pathway","PERP suppresses breast cancer metastasis via the ATF3–HSPA6 signaling pathway","","Objective: Clarify how the p53 apoptosis effector related to PMP-22 (PERP) regulates breast cancer metastasis. Methods: Assess PERP expression in breast cancer cell lines, public datasets, and 142 patient samples with RT–qPCR, western blotting, and immunohistochemistry, then test metastasis effects in vitro and in vivo after PERP overexpression or knockdown. Results: PERP is reduced in tumors; low levels predict poor prognosis. PERP induces ATF3, which binds the HSPA6 promoter and activates its transcription, and loss of ATF3 or HSPA6 abolishes PERP’s antimetastatic effects. Conclusions: The PERP–ATF3–HSPA6 axis is a key regulatory pathway and potential therapeutic target for metastatic breast cancer.",{"@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/perp-suppresses-breast-cancer-metastasis-via-the-atf3hspa6-signaling-pathway/448030/",{"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/perp-suppresses-breast-cancer-metastasis-via-the-atf3hspa6-signaling-pathway/448030.png","ImageObject",300,407,{"name":92,"@type":93},"Ivy","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-11-05","2026-09-29",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 research objective of this study?","Question",{"text":112,"@type":113},"To determine the role of PERP in breast cancer metastasis, including its clinical significance and underlying mechanisms.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How was PERP expression measured and validated?",{"text":117,"@type":113},"PERP expression was evaluated in breast cancer cell lines, public datasets, and 142 patient samples using RT–qPCR, western blotting, and immunohistochemistry.",{"name":119,"@type":110,"acceptedAnswer":120},"What signaling axis explains PERP’s antimetastatic effect?",{"text":121,"@type":113},"PERP upregulates ATF3, and ATF3 binds the HSPA6 promoter to activate HSPA6 transcription; disrupting ATF3 or HSPA6 eliminates PERP’s antimetastatic effects.","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},448030,1790877543,{"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":56,"language":139,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":140,"faqs":141,"seo_title":142,"seo_description":67,"update_tm":143,"read_time":144,"preview_page_count":4},549758252649,"https://ap-avatar.wpscdn.com/avatar/8000253669c5317157?_k=1778319167496531819","PERP suppresses breast cancer metastasis via the ATF3–HSPA6 signaling pathway  \nCaiping Chen, Chao Han, Li Xue, Wanxin Wu, Lin Zhang and Xiang Lu   \nJournal of International Medical Research 2025, Vol. 53(12) 1–19! The Author(s) 2025 Article reuse guidelines:  \n[sagepub.com/journals-permissions](sagepub.com/journals-permissions)[ ](sagepub.com/journals-permissions)[DOI: 10.1177/03000605251406800](DOI: 10.1177/03000605251406800)[ ](DOI: 10.1177/03000605251406800)[journals.sagepub.com/home/imr](journals.sagepub.com/home/imr)  \nAbstract  \nObjective: The role of the tumor suppressor p53 apoptosis effector related to PMP-22 (PERP) in breast cancer metastasis remains unclear. This study investigated PERP’s role in metastatic progression, its clinical significance, and the mechanisms underlying its effects.  \nMethods: PERP expression was assessed in breast cancer cell lines, public datasets, and 142 patient samples using real-time quantitative polymerase chain reaction (RT–qPCR), western blotting, and immunohistochemistry. In vitro migration and invasion assays as well as in vivo metastasis model were performed after PERP overexpression or knockdown in MDA-MB-231 and MCF-7 cells. The roles of activating transcription factor 3 (ATF3) and heat shock protein family A member 6 (HSPA6) were evaluated through small-interfering RNA–mediated modulation, RNA sequencing, western blotting, RT–qPCR, and chromatin immunoprecipitation.  \nResults: PERP expression was markedly reduced in breast cancer cells and tumor tissues compared with that in normal controls, and low PERP levels were associated with poor prognosis. PERP overexpression suppressed metastasis. Mechanistically, PERP upregulated ATF3 expression, and ATF3 bound to the HSPA6 promoter to activate its transcription. Knockdown of ATF3 or HSPA6 eliminated the antimetastatic effects of PERP.  \nConclusions: PERP suppresses breast cancer metastasis by inducing ATF3, which in turn activates HSPA6 transcription. This PERP–ATF3–HSPA6 axis represents a key regulatory pathway and serves as a potential therapeutic target in metastatic breast cancer.  \nKeywords  \nBreast neoplasms, p53 apoptosis effector related to PMP-22, activating transcription factor 3, heat shock protein family A member 6, neoplasm metastasis  \nDate received: 9 August 2025; accepted: 24 November 2025  \nAffiliated Hospital of Jiaxing University (First Hospital of Jiaxing), China  \nCorresponding author:  \nXiang Lu, Affiliated Hospital of Jiaxing University (First Hospital of Jiaxing), No. 1882 Zhonghuan South Road, Jiaxing, Zhejiang, 314001, China.  \nEmail: [00187649@zjxu.edu.cn](00187649@zjxu.edu.cn)  \nCreative Commons Non Commercial CC BY-NC: This article is distributed under the terms of the Creative  \nCommons Attribution-NonCommercial 4.0 License ([https://creativecommons.org/licenses/by-nc/4.0/](https://creativecommons.org/licenses/by-nc/4.0/)) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages ([https://us.sagepub.com/en-us/nam/open-access-at-sage](https://us.sagepub.com/en-us/nam/open-access-at-sage)).  \nIntroduction  \nBreast cancer is one of the most frequently diagnosed malignancies in women. In 2022, breast cancer constituted more than 2 . 3 million of the nearly 20 million new cancer cases worldwide, making it the second most prevalent cancer worldwide.1 Despite advances in medical technology that have improved survival rates, metastasis remains a major clinical challenge. Approximately 20%–30% of patients with early-stage breast cancer ultimately develop metastatic disease.2 Once metastasis occurs, prolonged treatments—often associated with side effects and high costs—are required; however, effective therapies remain limited due to inadequate understanding of the complex mechanisms underlying metastatic progression.  \np53 apoptosis effector related to PMP-22 (PERP), a transmembrane","cbCaiouPWRaf7xEX","https://ap.wps.com/l/cbCaiouPWRaf7xEX","pdf",2187267,"English","# Abstract\n## Objective\n## Methods\n## Results\n## Conclusions\n# Introduction\n# Methods\n## Bioinformatics analysis","[{\"question\":\"What is the main research objective of this study?\",\"answer\":\"To determine the role of PERP in breast cancer metastasis, including its clinical significance and underlying mechanisms.\"},{\"question\":\"How was PERP expression measured and validated?\",\"answer\":\"PERP expression was evaluated in breast cancer cell lines, public datasets, and 142 patient samples using RT–qPCR, western blotting, and immunohistochemistry.\"},{\"question\":\"What signaling axis explains PERP’s antimetastatic effect?\",\"answer\":\"PERP upregulates ATF3, and ATF3 binds the HSPA6 promoter to activate HSPA6 transcription; disrupting ATF3 or HSPA6 eliminates PERP’s antimetastatic effects.\"}]","PERP suppresses breast cancer metastasis via the ATF3–HSPA6 signaling pathway | PDF",1790724832,48]