RacGAP1 Plays an Oncogenic Role in Lung Adenocarcinoma - By Regulating the Wnt/β-Catenin Pathway

Sep 24, 2026

Uploaded by Adam

Lung adenocarcinoma (LUAD) is a leading cause of cancer incidence and mortality worldwide, while the RacGTPase activating protein RacGAP1 is known as an oncogenic factor in multiple malignancies yet remains unclear in LUAD. This study evaluates clinical relevance, oncogenic function, and molecular mechanisms using patient-cohort analyses and functional experiments. RacGAP1 is upregulated in tumors, predicts poor prognosis and survival, links to tobacco smoke, and promotes proliferation, migration, and invasion. Mechanistically, RacGAP1 correlates with Wnt-altered status and β-catenin, and its silencing reduces β-catenin transcriptional activity and Wnt gene expression (LGR5, Wnt2B, Wnt5A). Findings support an oncogenic RacGAP1 role via abnormal Wnt/β-catenin pathway activation and suggest therapeutic and diagnostic panel potential.

LanguageEnglish

CategoryHealthcare

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Pages16

Reading Time40 min

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Abstract

Introduction

Article RacGAP1 Plays an Oncogenic Role in Lung Adenocarcinoma by Regulating the Wnt/β-Catenin Pathway Nicola Mosca 1, Mariaceleste Pezzullo 1, Ilenia De Leo 1,2, Anna Truda 1,2, Giovanna Marchese 2,3, Aniello Russo 1 and Nicoletta Potenza 1, * Academic Editors: Eugenio Santos, Alberto Fernández-Medarde and Rosula Garcia-Navas Received: 15 April 2025 Revised: 20 May 2025 Accepted: 22 May 2025 Published: 23 May 2025 Citation: Mosca, N.; Pezzullo, M.; De Leo, I.; Truda, A.; Marchese, G.; Russo, A.; Potenza, N. RacGAP1 Plays an Oncogenic Role in Lung Adenocarcinoma by Regulating the Wnt/β-Catenin Pathway. Cells 2025, 14, 773. [https://doi.org/10.3390/](https://doi.org/10.3390/)[ ](https://doi.org/10.3390/)cells14110773 Copyright: © 2025 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://creativecommons.org/](https://creativecommons.org/)[ ](https://creativecommons.org/)[licenses/by/4.0/](licenses/by/4.0/)) . 1 Department of Environmental, Biological and Pharmaceutical Sciences and Technologies, University of Campania “Luigi Vanvitelli”, 81100 Caserta, Italy; [nicola.mosca@unicampania.it](nicola.mosca@unicampania.it) (N.M.); [mariaceleste.pezzullo@unicampania.it](mariaceleste.pezzullo@unicampania.it) (M.P.); [ilenia.deleo@unicampania.it](ilenia.deleo@unicampania.it) (I.D.L.); [anna.truda@unicampania.it](anna.truda@unicampania.it) (A.T.); [aniello.russo@unicampania.it](aniello.russo@unicampania.it) (A.R.) 2 Genomix 4Life S.r.l., 84081 Baronissi, Italy; [giovanna.marchese@genomix4life.com](giovanna.marchese@genomix4life.com) [3](3 Genome Research Center for Health-CRGS)[ Genome Research Center for Health-CRGS](3 Genome Research Center for Health-CRGS), [84081 Baronissi](84081 Baronissi), [Italy](Italy) * [Correspondence: nicoletta.potenza@unicampania.it](Correspondence: nicoletta.potenza@unicampania.it) Abstract: Lung cancer is the most diagnosed cancer and the primary cause of cancerrelated mortality worldwide, with lung adenocarcinoma (LUAD) becoming the prevalent histological subtype. Rac GTPase activating protein 1 (RacGAP1) has been found to be upregulated in several cancers, where it acts as an oncogene; nevertheless, its role in lung adenocarcinoma is largely unknown. The present study investigated the clinical relevance, the oncogenic function and the underlying molecular mechanisms of RacGAP1 in LUAD. Analyses of five patient cohorts’ datasets revealed that RacGAP1 was upregulated in adenocarcinoma tissues compared to normal lung tissues, and its overexpression was associated with unfavorable prognostic factors and poor survival; intriguingly, RacGAP1 expression was related to tobacco smoke, a well-known risk factor for LUAD. Then, experimental analyses demonstrated that RacGAP1 knockdown inhibited cell proliferation, migration and invasion, thus highlighting its role in promoting LUAD. Finally, the finding of significant correlations between RacGAP1 and Wnt-altered status or β-catenin in patients led to experiments demonstrating that silencing of RacGAP1 reduced β-catenin transcriptional activity, thereby downregulating the expression of Wnt-related genes, i.e., LGR5, Wnt2B and Wnt5A. Overall, our findings indicate that RacGAP1 plays an oncogenic role inadenocarcinoma, contributing to the abnormal activation of the Wnt/β-catenin signaling pathway. These findings may pave the way for innovative therapeutic strategies and the development of advanced diagnostic panels. Keywords: lung adenocarcinoma; GAP; GTPase activating protein; siRNA silencing; Wnt pathway 1. Introduction Lung cancer (LC) is the most diagnosed cancer, with 2.5 million new cases and 1.8 million new deaths reported worldwide in 2022 . It accounts for 12.4% of all cancer diagnosesand 18.7% of all cancer-related deaths. LC has the highest incidence and mortality rates among men and ran

FAQs

What is the main goal of the study on RacGAP1 in lung adenocarcinoma?

To determine the clinical relevance, oncogenic function, and underlying molecular mechanisms of RacGAP1 in LUAD.

How is RacGAP1 linked to patient outcomes in lung adenocarcinoma?

RacGAP1 is upregulated in adenocarcinoma tissues, and overexpression is associated with unfavorable prognostic factors and poor survival.

What molecular mechanism does the study propose for RacGAP1’s oncogenic role?

RacGAP1 is associated with Wnt-altered status and β-catenin, and RacGAP1 silencing reduces β-catenin transcriptional activity and downstream Wnt-related gene expression (LGR5, Wnt2B, Wnt5A).

Sep 24, 2026

Uploaded by Adam