Drosophila as Model System to Study Ras-Mediated Oncogenesis - The Case of the Tensin Family of Proteins

Sep 24, 2026

Oncogenic mutations in the small GTPase Ras account for about 30% of human cancers, yet Ras-driven tissue expansion is limited by oncogene-induced cellular senescence, requiring additional cooperating mutations for tumor progression. This work uses the Drosophila wing imaginal disc epithelium to analyze epithelial cancer progression by orthologs of human TNS2 and TNS4, blistery and PVRAP. Null PVRAP mutants are viable, and loss of either PVRAP or blistery enhances RasV12-mediated hyperplasia. The study also identifies a mechanism in which tensins restrict Ras oncogenic capacity through control of cell shape and growth, supporting an evolutionarily conserved tumor-modulating role.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages18

Reading Time45 min

AccessFree to download

Introduction

Ras-driven tumorigenesis and cooperation

Drosophila as a model for epithelial cancer

Wing imaginal disc and RasV12 hyperplasia

RNAi screen to identify modulators

Article Drosophila as Model System to Study Ras-Mediated Oncogenesis: The Case of the Tensin Family of Proteins Ana Mart½nez-Abarca Mill¡n †, Jennifer Soler Beatty †, Andrea Valencia Expâsito and Mar½a D. Mart½n-Bermudo * Citation: Martínez-Abarca Millán, A.; Soler Beatty, J.; Valencia Expósito, A.; Martín-Bermudo, M.D. Drosophila as Model System to Study Ras-Mediated Oncogenesis: The Case of the Tensin Family of Proteins. Genes 2023, 14, 1502. [https://](https://)[ ](https://)[doi.org/10.3390/genes14071502](doi.org/10.3390/genes14071502) [Academic Editors: Sergio Casas-Tint](Academic Editors: Sergio Casas-Tint)â and Luis Alberto Baena-Lâpez Received: 6 July 2023 Revised: 14 July 2023 Accepted: 18 July 2023 Published: 23 July 2023 Copyright: © 2023 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://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) . Centro Andaluz de Biolog½a del Desarrollo, Universidad Pablo de Olavide/CSIC/JA, Ctra Utrera Km1, 41013 Sevilla, Spain; [amtezmi@gmail.com](amtezmi@gmail.com) (A.M.-A.M.); [beattyjs.94@gmail.com](beattyjs.94@gmail.com) (J.S.B.); [andrea.ve06@gmail.com](andrea.ve06@gmail.com) (A.V.E.) * Correspondence: mdmarber@upo.es † These authors contributed equally to this work. Abstract: Oncogenic mutations in the small GTPase Ras contribute to ~30% of human cancers. However, tissue growth induced by oncogenic Ras is restrained by the induction of cellular senescence, and additional mutations are required to induce tumor progression. Therefore, identifying cooperating cancer genes is of paramount importance. Recently, the tensin family of focal adhesion proteins, TNS1-4, have emerged as regulators of carcinogenesis, yet their role in cancer appears somewhat controversial. Around 90% of human cancers are of epithelial origin. We have used the Drosophila wing imaginal disc epithelium as a model system to gain insight into the roles of two orthologs of human TNS2 and 4, blistery (by) and PVRAP, in epithelial cancer progression. We have generated null mutations in PVRAP and found that, as is the case for by and mammalian tensins, PVRAP mutants are viable. We have also found that elimination of either PVRAP or by potentiates RasV12-mediated wing disc hyperplasia. Furthermore, our results have unraveled a mechanism by which tensins may limit Ras oncogenic capacity, the regulation of cell shape and growth. These results demonstrate that Drosophila tensins behave as suppressors of Ras-driven tissue hyperplasia, suggesting that the roles of tensins as modulators of cancer progression might be evolutionarily conserved. Keywords: oncogenic Ras; overgrowth; tensins; Drosophila 1. Introduction Cancer is the second leading cause of death worldwide [1] . Cancer is characterized by the uncontrolled growth and spread of cells leading to invasion of normal tissues. Extensive research over the last few years has revealed that cancer is a genetically complex and heterogenous disease with each tumor carrying mutations not in a single gene but in several genes [2,3] . Thus, the isolation of factors collaborating with tumor progression is crucial to understand tumor development and malignancy. The Drosophila genome is 60% homologous to that of humans, and about 75% of genes responsible for human diseases have homologs in ﬂies [4] . This, combined with a short generation time, low maintenance costs and powerful genetic tools, makes the ﬂy an ideal model system to study cancer. About 90% of human cancers are of epithelial origin [5] . Epithelial tissues are composed of cells with an apico-basal polarity held together in sheets by specialized junctions. The apical face of the epithelial tissue is exposed to either the external environment or the b

FAQs

Why is identifying cooperating cancer genes important for Ras-driven cancers?

Ras oncogenic activity can initially trigger cellular senescence that restrains tissue growth. Additional mutations are therefore needed for tumor progression, making cooperating genes crucial to uncover.

What system and genetic approach were used to study tensins and Ras oncogenesis?

The study used the Drosophila wing imaginal disc epithelium as a model and generated null mutations in PVRAP. It also used genetic perturbations to test how PVRAP and blistery affect RasV12-mediated hyperplasia.

What conclusions does the paper draw about tensin function in Ras-driven overgrowth?

Tensins in Drosophila act as suppressors of Ras-driven tissue hyperplasia. The work supports a mechanism in which tensins limit Ras oncogenic capacity by regulating cell shape and growth.

Sep 24, 2026

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