Related Experiment Video

Updated: May 20, 2025

Monitoring Hippo Signaling Pathway Activity Using a Luciferase-based Large Tumor Suppressor LATS Biosensor
07:16

Monitoring Hippo Signaling Pathway Activity Using a Luciferase-based Large Tumor Suppressor LATS Biosensor

Published on: September 13, 2018

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Targeting the disrupted Hippo signaling to prevent neoplastic renal epithelial cell immune evasion

Xiangmin Lv1, Jiyuan Liu1, Jinpeng Ruan1

  • 1Vincent Center for Reproductive Biology, Department of Obstetrics and Gynecology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.

Nature Communications
|March 25, 2025
PubMed

Insights

Hyperactivating YAP1 in kidney cells drives papillary renal cell carcinoma (pRCC) development by promoting cell transformation and myeloid-derived suppressor cell (MDSC) accumulation. Targeting YAP1 or MDSCs offers potential therapeutic strategies for pRCC.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Papillary renal cell carcinoma (pRCC) is linked to deletions in Hippo/YAP pathway tumor suppressors.
  • The Hippo/YAP signaling pathway's role in pRCC pathogenesis requires further elucidation.

Purpose of the Study:

  • To investigate the role of YAP1 hyperactivation in pRCC development using a transgenic mouse model.
  • To analyze cellular landscape changes during YAP1-induced pRCC initiation and progression.

Main Methods:

  • Development of a renal epithelial cell-specific YAP1 hyperactivation transgenic mouse model.
  • Single-cell resolution analysis of cellular alterations during cancer development.
  • Assessment of myeloid-derived suppressor cells (MDSCs) and evaluation of TEAD inhibitor (MGH-CP1) efficacy.

Main Results:

  • YAP1 hyperactivation induces renal tubular epithelial cell dedifferentiation and transformation, leading to pRCC.
  • YAP1 manipulation alters multiple signaling pathways, promotes MDSC accumulation, and drives pRCC development.
  • MDSC depletion inhibits YAP1-induced kidney overgrowth and tumorigenesis; MGH-CP1 suppresses tumor development by impeding MDSC accumulation.

Conclusions:

  • Disrupted Hippo/YAP signaling is a significant driver of pRCC.
  • Targeting the Hippo pathway, including YAP1 and MDSCs, presents a viable therapeutic strategy for pRCC prevention and treatment.

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