Gene therapy for diffuse pleural mesotheliomas in preclinical models by concurrent expression of NF2 and SuperHippo

Diffuse pleural mesothelioma (DPM) is a lethal cancer with a poor prognosis and limited treatment options. The Hippo signaling pathway genes, such as NF2 and LATS1/2, are frequently mutated in DPM, indicating a tumor suppressor role in the development of DPM. Here, we show that in DPM cell lines lacking NF2 and in mice with a conditional Nf2 knockout, downregulation of WWC proteins, another family of Hippo pathway regulators, accelerates DPM progression. Conversely, the expression of SuperHippo, a WWC-derived minigene, effectively enhances Hippo signaling and suppresses DPM development. Moreover, the adeno-associated virus serotype 6 (AAV6) has been engineered to deliver both NF2 and SuperHippo genes into mesothelial cells, which substantially impedes tumor growth in xenograft and genetic DPM models and prolongs the median survival of mice. These findings serve as a proof of concept for the potential use of gene therapy targeting the Hippo pathway to treat DPM.

Authors

Institutions

Publication Details

Journal
Cell Reports Medicine
Published
2024-10-01
DOI
https://doi.org/10.1016/j.xcrm.2024.101763
Citations
8
Primary Topic
Hippo pathway signaling and YAP/TAZ
Type
article
Field-Weighted Citation Impact
2.61

Funders

Controls
|||
ALL TIME
JAN
FEB
MAR
APR
MAY
JUN
JUL
AUG
SEP
OCT
article

Gene therapy for diffuse pleural mesotheliomas in preclinical models by concurrent expression of NF2 and SuperHippo

Yuan Gu, Dan Ye, Zhenxing Zhong, Ruxin Jin et al.
8 citations
Cell Reports Medicine
Hippo pathway signaling and YAP/TAZ
2.61
article

Gene therapy for diffuse pleural mesotheliomas in preclinical models by concurrent expression of NF2 and SuperHippo

Yuan Gu, Dan Ye, Zhenxing Zhong, Ruxin Jin, Xincheng Liu, Fa‐Xing Yu, Sixian Qi, Ling Chen, Kang Chen, Rui Zhu, Xu Zhang, Yu Wang
article en
8 citations

Abstract

Diffuse pleural mesothelioma (DPM) is a lethal cancer with a poor prognosis and limited treatment options. The Hippo signaling pathway genes, such as NF2 and LATS1/2, are frequently mutated in DPM, indicating a tumor suppressor role in the development of DPM. Here, we show that in DPM cell lines lacking NF2 and in mice with a conditional Nf2 knockout, downregulation of WWC proteins, another family of Hippo pathway regulators, accelerates DPM progression. Conversely, the expression of SuperHippo, a WWC-derived minigene, effectively enhances Hippo signaling and suppresses DPM development. Moreover, the adeno-associated virus serotype 6 (AAV6) has been engineered to deliver both NF2 and SuperHippo genes into mesothelial cells, which substantially impedes tumor growth in xenograft and genetic DPM models and prolongs the median survival of mice. These findings serve as a proof of concept for the potential use of gene therapy targeting the Hippo pathway to treat DPM.

Cell Reports MedicineVol. 5(10)
Shanghai Medical College of Fudan University (CN), Wayne State University (US), Fudan University (CN), The Barbara Ann Karmanos Cancer Institute (US), Zhongshan Hospital (CN), Children's Hospital of Fudan University (CN), State Key Laboratory of Genetic Engineering
Shanghai Municipal Health Commission, National Natural Science Foundation of China, Ministry of Science and Technology of the People's Republic of China, Fudan University, Science and Technology Commission of Shanghai Municipality
Openalex Percentile: Top 10%
Hippo pathway signaling and YAP/TAZ
2.61
DOIOpen Access PDFOpenAlex
AI Navigator

Ask Laika to Summarize, Analyze, and Connect papers live on the map.

Summarize Papers & Methodologies

Extract key findings, datasets, and comparative methods across publications.

Benchmark Rankings & Visual Analytics

Rank top research institutions, authors, funders, topics, and journals by Field-Weighted Citation Impact (FWCI) and paper volume with instant charts.

Connect Distant Disciplines

Bridge topological clusters on the map to find hidden collaborative intersections.