PARVA promotes gastric cancer progression through FBXO15-related PI3K/AKT signaling

doi:10.4251/wjgo.121827

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World Journal of Gastrointestinal Oncology

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1948-5204

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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

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Copyright: ©Author(s) 2026. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution-NonCommercial (CC BY-NC 4.0) license. No commercial re-use. See permissions. Published by Baishideng Publishing Group Inc.

World J Gastrointest Oncol. Oct 15, 2026; 18(10): 121827
Published online Oct 15, 2026. doi: 10.4251/wjgo.121827

PARVA promotes gastric cancer progression through FBXO15-related PI3K/AKT signaling

Xu Lu, Jing Li, Ming-Liang Wang, Hui-Zhen Wang, Yong-Xiang Li

Xu Lu, Jing Li, Ming-Liang Wang, Hui-Zhen Wang, Yong-Xiang Li, Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Institute of General Surgery of Anhui Medical University, Hefei 230000, Anhui Province, China

Xu Lu, Department of General Surgery, The Affiliated Chuzhou Hospital of Anhui Medical University, The First People’s Hospital of Chuzhou, Chuzhou 239000, Anhui Province, China

Author contributions: Li YX designed and supervised the study; Lu X performed most of the experiments and drafted the manuscript; Wang HZ participated in data analysis and manuscript revision; Li J and Wang ML contributed to cell culture, in vitro functional assays, and data collection; and all authors contributed to data interpretation, reviewed the manuscript, and approved the final version.

AI contribution statement: A portion of the response to reviewers was prepared with the assistance of ChatGPT (OpenAI; GPT-5.5 Thinking). The AI tool was used only for language polishing, formatting assistance, wording support, and organization of the point-by-point response letter. The scientific content, responses to reviewers, interpretation of data, revision decisions, and final approval were provided, checked, and revised by the authors. No AI tool was used to generate research data, perform statistical analysis, interpret results, formulate conclusions, or prepare references. All AI-assisted text was critically reviewed and revised by the authors, who take full responsibility for the accuracy, originality, and integrity of the manuscript and the response to reviewers.

Supported by the University Fund Project of Anhui Medical University, No. 2023xkj093.

Institutional review board statement: The study as reviewed and approved by the Biomedical Ethics Committee of Anhui Medical University (Approval No. 20180323).

Institutional animal care and use committee statement: All animal experiments were reviewed and approved by the Institutional Animal Care and Use Committee of Anhui Medical University (Approval No. LLSC20180345).

Conflict-of-interest statement: The authors declare that they have no conflict of interest.

ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.

Data sharing statement: The raw data generated in this study have been deposited in the ProteomeXchange database and the National Center for Biotechnology Information under accession numbers PXD069269, PRJNA1338994 and PRJNA1462142, respectively. No custom code or scripts were used in this study.

Corresponding author: Yong-Xiang Li, Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Institute of General Surgery of Anhui Medical University, No. 218 Jixi Road, Shushan District, Hefei 230000, Anhui Province, China. liyongxiang@ahmu.edu.cn

Received: April 2, 2026
Revised: May 8, 2026
Accepted: May 28, 2026
Published online: October 15, 2026
Processing time: 169 Days and 1.3 Hours

Abstract

BACKGROUND

Gastric cancer (GC) remains a major cause of cancer-related death worldwide, and effective molecular targets for advanced disease are still limited. PARVA (alpha-parvin) is a focal adhesion-associated protein involved in cell-matrix interaction and cytoskeletal regulation, but its role in GC remains unclear.

AIM

To investigate the expression, biological function, and potential mechanism of PARVA in GC.

METHODS

PARVA was identified from our previous proteomic screening and further evaluated using public databases. Its expression was validated in GC tissues and cell lines by quantitative real-time PCR, Western blotting, and immunohistochemistry. A tissue microarray containing 107 GC tissues and 22 adjacent normal tissues was used to assess expression and survival association. Gain- and loss-of-function assays were performed to evaluate proliferation, migration, and invasion. RNA sequencing, rescue experiments, and a nude mouse xenograft model were used to explore the underlying mechanism involving FBXO15 and PI3K/AKT signaling.

RESULTS

PARVA was upregulated in GC tissues and cell lines, and high PARVA expression was associated with shorter overall survival. Single-cell analysis showed heterogeneous PARVA expression, with relatively higher levels in fibroblast- and myofibroblast-related populations. Functionally, PARVA knockdown suppressed cell proliferation, migration, and invasion, whereas PARVA overexpression had the opposite effects. In vivo, PARVA silencing inhibited xenograft growth. Mechanistically, RNA sequencing showed significant enrichment of the PI3K/AKT pathway after PARVA knockdown. FBXO15 was identified as a candidate downstream effector, and rescue experiments showed that it partially reversed the effects of PARVA knockdown on malignant phenotypes and pathway activation.

CONCLUSION

PARVA is upregulated in GC and may promote malignant progression partly through FBXO15-related activation of the PI3K/AKT pathway.

Keywords: Gastric cancer; PARVA; FBXO15; PI3K/AKT; Proliferation; Migration; Invasion

Core Tip: PARVA was identified from previous proteomic screening and validated in gastric cancer. PARVA was upregulated in tumor tissues and cell lines, and high expression was associated with shorter overall survival. Functional assays showed that PARVA promoted proliferation, migration, invasion, and xenograft growth. Mechanistically, PARVA was associated with FBXO15 and activation of the PI3K/AKT pathway. These findings support PARVA as a candidate biomarker and potential therapeutic target requiring further validation.