Identiﬁcation of matrix-remodeling associated 5 as a possible molecular oncotarget of pancreatic cancer

Sep 24, 2026

Pancreatic cancer shows extremely poor prognosis. Expression profiling and bioinformatics analyses indicate MXRA5 transcripts are markedly elevated in pancreatic cancer tissues and associate with poor overall survival and advanced clinicopathologic features. MXRA5 mRNA and protein are increased across microarray samples and pancreatic cancer cell lines. MXRA5 knockdown or knockout reduces survival, proliferation, migration, invasion, and EMT while triggering apoptosis; overexpression produces the opposite effects. Mechanistically, MXRA5 drives PI3K-Akt-mTOR cascade activity, and suppresses tumor growth in vivo. MXRA5 therefore emerges as a potential therapeutic oncotarget via EMT and Akt-mTOR activation.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages14

Reading Time35 min

AccessFree to download

Introduction

Materials and Methods

Bioinformatics analysis

[www.nature.com/cddis](www.nature.com/cddis) ARTICLE OPEN Identiﬁcation of matrix-remodeling associated 5 as a possible molecular oncotarget of pancreatic cancer Shi-qing Peng 1,4, Xiao-ren Zhu1,4, Ming-zhi Zhao2,4, Yi-fan Zhang3,4, An-ran Wang1,4, Min-bin Chen 1 ✉ and Zhen-yu Ye 3 ✉ © The Author(s) 2023 | | | | | | --- | --- | --- | --- | | | Pancreatic cancer has an extremely poor prognosis. Here we examined expression, potential functions and underlying mechanisms of MXRA5 (matrix remodeling associated 5) in pancreatic cancer. Bioinformatics studies revealed that MXRA5 transcripts are signiﬁcantly elevated in pancreatic cancer tissues, correlating with the poor overall survival, high T-stage, N1 and pathologic stage of the patients. MXRA5 mRNA and protein expression is signiﬁcantly elevated in microarray pancreatic cancer tissues and different pancreatic cancer cells. In primary and immortalized (BxPC-3 and PANC-1 lines) pancreatic cancer cells, shRNA-induced
MXRA5 silencing or CRISPR/Cas9-mediated MXRA5 knockout suppressed cell survival, proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT), while provoking cell apoptosis. Conversely, forced overexpression of MXRA5 further promoted pancreatic cancer cell progression and EMT. Bioinformatics studies and the protein chip analyses revealed that differentially expressed genes (DEGs) and differentially expressed proteins (DEPs) in MXRA5-overexpressed primary pancreatic cancer cells were enriched in the PI3K-Akt-mTOR cascade. Indeed, Akt-mTOR activation in primary human pancreatic cancer cells was inhibited by MXRA5 shRNA or knockout, but was augmented following MXRA5 overexpression. In vivo, the growth of MXRA5 KO PANC-1 xenografts was largely inhibited in nude mice. Moreover, intratumoral injection of adeno-associated virus-packed MXRA5 shRNA potently inhibited primary pancreatic cancer cell growth in nude mice. Akt-mTOR activation was also largely inhibited in the MXRA5-depleted pancreatic cancer xenografts. Contrarily MXRA5 overexpression promoted primary pancreatic cancer cell growth in nude mice. Together, overexpressed MXRA5 is important for pancreatic cancer cell growth possibly through promoting EMT and Akt-mTOR activation. MXRA5 could be a potential therapeutic oncotarget for pancreatic cancer. | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | Cell Death and Disease (2023)14:157; [https://doi.org/10.1038/s41419-023-05684-5](https://doi.org/10.1038/s41419-023-05684-5) | | | | | | | | INTRODUCTION Pancreatic cancer is one of the most lethal malignancy worldwide [1, 2] . The 5-year overall survival of pancreatic cancer patients is less than 10%[3, 4] . Patients with advanced and/or metastatic pancreatic cancer often have extremely poor prognosis [1, 5] . Current treatment strategies, including surgery, radiotherapy and gemcitabine-based chemotherapy, failed to signiﬁcantly improve survival and prognosis of advanced patients [6, 7] . It is often diagnosed at the advanced stages with cancer local inﬁltration and/ or systematic metastasis [3] . Therefore, novel and more effective molecular-targeted therapies are urgently needed [8–10] . Extracellular matrix (ECM) is vital for cancer cell growth, metastasis and epithelial-to-mesenchymal cell transition (EMT)[11–14] . Cancer cells undergo invasion and metastasis through EMT that latter could be activated by ECM-related proteins and enzymes [15–17] . ECM also serves as nutrition source, promoting pancreatic cancer cell survival and proliferation under nutrition-low conditions [18] . Studies have shown that ECM is a key factor for tumorigenesis and the progression of pancreatic cancer [6, 7, 19] . Matrix-remodeling associated (MXRA) protein family proteins, including MXRA5, MXRA7 and MXRA8, are importa

FAQs

What is MXRA5 and how is it related to pancreatic cancer in this study?

MXRA5 is investigated for its expression level, functions, and molecular mechanisms in pancreatic cancer. MXRA5 transcripts, mRNA, and protein are reported as significantly elevated in pancreatic cancer tissues and cell lines.

How does altering MXRA5 expression affect pancreatic cancer cell behavior?

shRNA silencing or CRISPR/Cas9 knockout of MXRA5 suppresses survival, proliferation, migration, invasion, and EMT while increasing apoptosis. Forced overexpression of MXRA5 promotes progression and EMT.

What pathway is implicated in MXRA5’s pro-cancer effects, and what evidence supports it?

Differential genes and proteins in MXRA5-overexpressed cells are enriched in the PI3K-Akt-mTOR cascade. Akt-mTOR activation is inhibited by MXRA5 shRNA/knockout and augmented by MXRA5 overexpression, including in xenograft models.

Sep 24, 2026

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