VMP1 inhibits the progression of breast cancer - regulating PI3K/AKT and MEK/ERK signaling pathway

Sep 22, 2026

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Vacuolar membrane protein 1 (VMP1), an endoplasmic reticulum-resident multi-spanning membrane protein, has unclear biological functions in breast cancer. The study profiles VMP1 expression and validates it with Western blot, qRT-PCR, and single-cell analysis, then tests functional effects using knockdown, overexpression, proliferation, colony formation, migration assays, and in vivo tumor growth. Clinical analysis of 117 patient samples links VMP1 expression with molecular subtypes. Mechanistically, VMP1 modulates PI3K/AKT and MEK/ERK signaling, influencing tumor malignancy and progression.

LanguageEnglish

CategoryHealthcare

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Pages13

Reading Time33 min

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Abstract

Background

Methods

Results

Conclusions

Introduction

Chen et al. Cancer Cell International (2026) 26:57 [https://doi.org/10.1186/s12935-025-04149-3](https://doi.org/10.1186/s12935-025-04149-3) Cancer Cell International RESEARCH Open Access VMP1 inhibits the progression of breast cancer via regulating PI3K/AKT and MEK/ERK signaling pathway Shuzhao Chen1†, Yuanke Liang1†, Huan Chen2†, Chengyu Wu1, Zhenhao Wang1, RuiqianYang1, Xinqiang Fang1, Yanyang Ma1, Haoyu Lin1* and Xiaolong Wei3* Abstract Background Vacuolar membrane protein 1 (VMP1) is an endoplasmic reticulum- resident and multi-spanning membrane protein involved in various human cancers. However, its biological functions and molecular mechanisms in breast cancer remain underexplored. Methods Gene expression profiling was used to determine VMP1 levels. Western blot, qRT-PCR, and single cell analysis were employed to confirm the findings. Functional assays such as knockdown and overexpression experiments were carried out to assess the effects on cell proliferation, colony formation, and migration. In vivo tumor growth experiments were also conducted. Additionally, clinical analysis of 117 breast cancer patient samples was performed to study the correlation between VMP1 expression and molecular subtypes. Results VMP1 was significantly upregulated in MCF − 7 cells line. Knockdown of VMP1 enhanced cell proliferation, colony formation, and migration, while overexpression suppressed tumor cell malignancy and inhibited tumor growth in vivo. Mechanistically, VMP1 was found to regulate key oncogenic signaling pathways, including PI3K/AKT and MEK/ERK. Clinical analysis showed that VMP1 expression was correlated with molecular subtypes. Conclusions In conclusion, our findings suggest that VMP1 plays a crucial role in breast cancer progression, and modulation of its expression or activity may offer a therapeutic strategy. Keywords Vacuole membrane protein 1, Breast cancer, PI3K/AKT and MEK/ERK pathways , Tumor progression †Shuzhao Chen, Yuanke Liang and Huan Chen equal contribution. *Correspondence: Haoyu Lin [rainlhy@stu.edu.cn](rainlhy@stu.edu.cn)[ ](rainlhy@stu.edu.cn)Xiaolong Wei [weixiaolonghh@126.com](weixiaolonghh@126.com) 1Department of Thyroid and Breast Surgery, Clinical Research Center, The First Affiliated Hospital of Shantou University Medical College (SUMC), 57 Changping Road, Shantou 515000, China 2Shenshan Medical Centre, Memorial Hospital of SunYat-sen University, Shanwei 516600, China 3Department of Pathology, Cancer Hospital of Shantou University Medical College, 7 Raoping Road, Shantou 515000, China Introduction Breast cancer is the most commonly diagnosed malignancy in women and one in six cancer deaths worldwide in women [1]. Despite significant progress in early detection and the development of targeted therapies, breast cancer remains a leading cause of cancer mortality. Recurrence and metastasis continue to present major clinical challenges, underscoring the need for a deeper understanding of the mechanisms driving tumor progression [2]. These challenges emphasize the critical need to uncover novel molecular mechanisms and therapeutic targets to improve patient outcomes. © The Author(s) 2026. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use

FAQs

What is the main finding about VMP1 in breast cancer progression?

VMP1 is significantly upregulated in MCF-7 cells. Reducing VMP1 enhances proliferation, colony formation, and migration, while increasing VMP1 suppresses malignancy and inhibits tumor growth in vivo.

Which signaling pathways does VMP1 regulate?

VMP1 regulates key oncogenic pathways including PI3K/AKT and MEK/ERK, linking VMP1 expression to tumor-promoting signaling activity.

How is VMP1 related to clinical subtypes of breast cancer?

Analysis of 117 patient samples shows that VMP1 expression correlates with molecular subtypes, supporting clinical relevance beyond cell and animal models.

Sep 22, 2026

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