MXRA5 promotes the progression and metastasis of breast cancer via activation of the epithelial-to-mesenchymal transition pathway

Sep 23, 2026

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. 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.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages14

Reading Time35 min

AccessFree to download

Introduction

Methods and multi-omics analysis

MXRA5 expression and clinical significance

Correlation with metastasis and prognosis

Functional validation

In vitro effects

In vivo metastasis results

Mechanistic pathway

PI3K/AKT/mTOR activation and EMT

Korean J Physiol Pharmacol 2026;30(5):487-500 [https://doi.org/10.4196/kjpp.25.435](https://doi.org/10.4196/kjpp.25.435) Original Article ~~ ~~MXRA5 promotes the progression and metastasis of breast cancer via activation of the epithelial-to-mesenchymal transition pathway Jian Wang1,2,\#, Jie Tang3,\#, andYaoxin Wang1,* 1Department 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 ARTICLE INFO Received December 13, 2025 Revised March 29, 2026 Accepted April 7, 2026 Published online September 1, 2026 *Correspondence Yaoxin Wang [E-mail: wangyaoxin@ws-hospital.sh.cn](E-mail: wangyaoxin@ws-hospital.sh.cn) [https://orcid.org/0009-0006-7263-4573](https://orcid.org/0009-0006-7263-4573) KeyWords Breast neoplasms Cell proliferation Epithelial-mesenchymal transition MXRA5 protein Neoplasm metastasis \#These authors contributed equally to this work. ABSTRACT 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. INTRODUCTION Breast 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 breast 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. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial

FAQs

What role does MXRA5 play in breast cancer progression and metastasis?

MXRA5 promotes aggressive tumor behavior by activating the PI3K/AKT/mTOR signaling axis, which drives EMT and supports proliferation, migration, invasion, and metastasis.

How is MXRA5 expression related to clinical outcomes in breast cancer?

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.

What are the key experimental findings from silencing MXRA5?

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.

Sep 23, 2026

Uploaded by LangkahRina