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Updated: May 16, 2025

Methods for Evaluating the Role of c-Fos and Dusp1 in Oncogene Dependence
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Published on: January 7, 2019

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DEPTOR suppresses lymphomagenesis by promoting EGFR degradation via HUWE1 E3 ligase

Xiufang Xiong1,2,3,4, Xiaoyu Chen5, Shengpeng Shao6,7,8

  • 1Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China. xiufang@zju.edu.cn.

Cell Death and Differentiation
|April 1, 2025
PubMed

Insights

DEPTOR acts as a tumor suppressor in lymphoma development. Loss of DEPTOR accelerates lymphoma, while its reactivation may offer a novel therapeutic strategy for this cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • DEPTOR is an mTOR inhibitor involved in tumorigenesis and frequently dysregulated in cancers.
  • DEPTOR's role in lymphomagenesis is not well understood, with context-dependent tumor suppressor or oncogenic functions.
  • Dysregulation of DEPTOR is observed in various human cancers, suggesting its potential involvement in lymphoma.

Purpose of the Study:

  • To investigate the role of DEPTOR in lymphomagenesis.
  • To elucidate the molecular mechanisms by which DEPTOR regulates lymphoma development.
  • To assess the therapeutic potential of targeting DEPTOR in lymphoma.

Main Methods:

  • Utilized a mouse lymphoma model with heterozygous Pten loss.
  • Generated and analyzed mice with Deptor knockout (KO) and a degradation-resistant Deptor knock-in (KI) variant (DeptorS275A).
  • Examined DEPTOR protein levels in human lymphoma tissues and normal lymph nodes.

Main Results:

  • Deptor KO accelerated lymphomagenesis and shortened lifespan in Pten-loss mice.
  • The degradation-resistant DeptorS275A KI variant significantly inhibited lymphomagenesis.
  • Lower DEPTOR protein levels were observed in human lymphoma tissues compared to normal lymph nodes.
  • Mechanistically, DEPTOR enhances EGFR ubiquitination and degradation, inactivating MAPK signaling, and also inhibits mTORC1 and mTORC2 signaling.

Conclusions:

  • DEPTOR functions as a tumor suppressor in Pten-loss-induced lymphomagenesis.
  • Reactivating DEPTOR presents a promising therapeutic strategy for lymphoma treatment.

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