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Oncogenic KRAS effector USP13 promotes metastasis in non-small cell lung cancer through deubiquitinating β-catenin

Yanguan Guo1, Jiaxin Tian2, Yongjian Guo2

  • 1School of Biopharmacy, China Pharmaceutical University, Nanjing 211198, P.R. China; Department of General Surgery and Department of Thoracic Surgery, The First Affiliated Hospital of Jinan University, Guangzhou 510632, P.R. China.

Cell Reports
|December 3, 2023
PubMed

Insights

Researchers identified USP13 as a key driver of metastasis in KRAS-mutant non-small cell lung cancer (NSCLC). Targeting USP13 with 2-methoxyestradiol offers a potential new treatment strategy for advanced NSCLC patients.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • KRAS mutations are common in non-small cell lung cancer (NSCLC), but treatments for many KRAS-mutant NSCLCs remain limited.
  • Developing targeted therapies requires understanding KRAS effectors that drive poor prognosis.

Purpose of the Study:

  • To identify novel therapeutic targets for KRAS-mutant NSCLC.
  • To investigate the role of KRAS-driven effectors in NSCLC metastasis.

Main Methods:

  • Investigated the role of deubiquitinase USP13 in KRAS-driven NSCLC.
  • Examined the mechanism of USP13 in regulating β-catenin and TCF4 interaction.
  • Screened a natural compound library for USP13 inhibitors.

Main Results:

  • KRAS signaling upregulates USP13 expression via RREB1.
  • Elevated USP13 promotes NSCLC metastasis and is linked to poor patient prognosis.
  • USP13 deubiquitinates β-catenin, enhancing its binding to TCF4.
  • 2-methoxyestradiol effectively inhibits USP13 and suppresses NSCLC metastasis in vitro and in vivo.

Conclusions:

  • USP13 is a KRAS effector that promotes metastasis in NSCLC.
  • USP13 is a potential therapeutic target for KRAS-mutant metastatic NSCLC.
  • 2-methoxyestradiol shows promise as a treatment for KRAS-mutant NSCLC.
Keywords:
CP: CancerNSCLCUSP13deubiquitinationmetastasisβ-catenin

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