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Multi-omics and in vitro assays showed MXRA5 is upregulated and correlates with advanced lymph node metastasis and poor prognosis, especially in Luminal B and HER2+ subtypes. Silencing MXRA5 reduces proliferation, migration, invasion, and lung metastasis. Mechanistically, MXRA5 activates the PI3K/AKT/mTOR axis to drive EMT, supporting MXRA5 as an oncogenic driver, prognostic biomarker, and therapeutic target.",{"@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/mxra5-promotes-the-progression-and-metastasis-of-breast-cancer-via-activation-of-the-epithelial-to-mesenchymal-transition-pathway/358011/",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/mxra5-promotes-the-progression-and-metastasis-of-breast-cancer-via-activation-of-the-epithelial-to-mesenchymal-transition-pathway/358011.png","ImageObject",300,407,{"name":42,"@type":43},"LangkahRina","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-10-29","2026-09-23",true,{"@type":52,"interactionType":53,"userInteractionCount":55},"InteractionCounter",{"@type":54},"ViewAction",14,{"@type":57,"mainEntity":58},"FAQPage",[59,65,69],{"name":60,"@type":61,"acceptedAnswer":62},"What 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\nOriginal Article ~~  ~~MXRA5 promotes the progression and metastasis of breast cancer via activation of the epithelial-to-mesenchymal transition pathway  \nJian Wang1,2,\\#, Jie Tang3,\\#, andYaoxin Wang1,*  \n1Department of Clinical Laboratory, Wusong Central Hospital, Baoshan District, Shanghai 200940, China, 2Clinical Research Center, Shanghai Eighth People’s Hospital, Shanghai 200235, China, 3Department of General Surgery, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China  \nARTICLE INFO  \nReceived December 13, 2025  \nRevised March 29, 2026  \nAccepted April 7, 2026  \nPublished online September 1, 2026  \n*Correspondence  \nYaoxin Wang  \n[E-mail: wangyaoxin@ws-hospital.sh.cn](E-mail: wangyaoxin@ws-hospital.sh.cn)  \n[https://orcid.org/0009-0006-7263-4573](https://orcid.org/0009-0006-7263-4573)  \nKeyWords  \nBreast neoplasms Cell proliferation  \nEpithelial-mesenchymal transition MXRA5 protein  \nNeoplasm metastasis  \n\\#These authors contributed equally to this work.  \nABSTRACT Breast cancer remains a primary cause of cancer-associated death globally, largely due to distant metastasis and therapeutic resistance. While matrix remodeling associated 5 (MXRA5) has been implicated in inflammation and fibrosis, its specific biological function and mechanistic role in breast cancer progression remain unclear. Herein, multi-omics analysis and in vitro functional assays were employed to investigate the expression pattern, clinical significance, and biological function of MXRA5 within breast cancer. We observed that MXRA5 was considerably upregulated within breast cancer tissues in comparison with normal controls at both mRNA and protein levels. Crucially, elevated MXRA5 expression exhibited a positive correlation with advanced lymph node metastasis and impaired clinical prognosis, including overall survival, disease-specific survival, and progression-free interval, particularly within the Luminal B and HER2+ subtypes. Functional validation demonstrated that MXRA5 silencing markedly repressed the abilities of BT474 and MDA-MB-361 cells to proliferate, to migrate, and to invade in vitro, and significantly reduced lung metastasis in vivo. Mechanistically, bioinformatics analysis and pharmacological rescue experiments demonstrated that MXRA5 promotes tumor aggressiveness by activating the PI3K/AKT/mTOR signaling axis, which subsequently drives the epithelial-tomesenchymal transition (EMT) pathway, evidenced by the positive regulation of key EMT transcription factors Snail and Twist, as well as the mesenchymal marker Vimentin. Collectively, these findings identify MXRA5 as a novel oncogenic driver in breast carcinoma and reveal its potential as a valuable prognostic biomarker and therapeutic target for managing metastatic disease.  \nINTRODUCTION  \nBreast cancer represents one of the most prevalent malignancies worldwide and stands as a primary cause of cancer-associated mortality among women [1,2]. Although advancements in screening and therapeutic modalities, including surgical resection, chemotherapy, and targeted molecular therapies have improved survival rates for early-stage disease [3], advanced or metastatic  \nbreast cancer patients’ prognosis remains largely unfavorable [4,5]. The clinical management of these patients is frequently hindered by tumor heterogeneity, drug resistance, and the inability of current standard-of-care treatments to effectively halt the progression of distant metastasis to major organs including the lung, bone, and brain [6-8]. Hence, to identify innovative therapeutic targets and prognostic biomarkers driving this metastatic cascade to improve patient outcomes is urgently needed.  \nThis is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial","cbCaimRQFBwO56wO","https://ap.wps.com/l/cbCaimRQFBwO56wO","pdf",13996781,"English","# Introduction\n# Methods and multi-omics analysis\n# MXRA5 expression and clinical significance\n## Correlation with metastasis and prognosis\n# Functional validation\n## In vitro effects\n## In vivo metastasis results\n# Mechanistic pathway\n## PI3K/AKT/mTOR activation and EMT","[{\"question\":\"What role does MXRA5 play in breast cancer progression and metastasis?\",\"answer\":\"MXRA5 promotes aggressive tumor behavior by activating the PI3K/AKT/mTOR signaling axis, which drives EMT and supports proliferation, migration, invasion, and metastasis.\"},{\"question\":\"How is MXRA5 expression related to clinical outcomes in breast cancer?\",\"answer\":\"MXRA5 is upregulated in breast cancer tissues at both mRNA and protein levels and higher expression positively correlates with advanced lymph node metastasis and poorer survival outcomes.\"},{\"question\":\"What are the key experimental findings from silencing MXRA5?\",\"answer\":\"MXRA5 silencing markedly represses the proliferation, migration, and invasion of BT474 and MDA-MB-361 cells in vitro and significantly reduces lung metastasis in vivo.\"}]","MXRA5 promotes the progression and metastasis of breast cancer via activation of the epithelial-to-mesenchymal transition pathway | PDF",1790132522,35]