LASS2 enhances p53 protein stability and nuclear import to suppress liver cancer progression through interaction with

Qingqing Zhao1, Wei He2,3, Zhouheng Liu2,3

  • 1Department of General Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, China.

Cell Death Discovery
|November 14, 2023
PubMed

Insights

LASS2 acts as a tumor suppressor in liver cancers like hepatocellular carcinoma (HCC) by stabilizing p53. This discovery reveals a new mechanism for targeting liver cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • LASS2 is a known tumor suppressor in hepatocellular carcinoma (HCC), but its precise mechanisms in HCC, cholangiocarcinoma (CCA), and hepatoblastoma (HB) are not well understood.
  • Limited research exists on the downstream effects and specific roles of LASS2 in various primary liver cancers.

Purpose of the Study:

  • To elucidate the tumor-suppressive mechanism of LASS2 in liver cancer.
  • To investigate the role of LASS2 in regulating p53 signaling pathway.
  • To explore LASS2 as a potential therapeutic target for liver cancer.

Main Methods:

  • Overexpression of LASS2 in hepatoma cell lines (HepG2, HCCLM3, HuCCT1).
  • Gene set enrichment analysis to identify affected pathways.
  • Correlation analysis of LASS2 expression with TNM stage and p53 acetylation in tumor tissues.
  • Investigation of LASS2 interaction with MDM2/MDMX and its effect on p53.

Main Results:

  • LASS2 overexpression inhibited proliferation, migration, invasion, and induced apoptosis in hepatoma cells.
  • Gene set enrichment analysis revealed LASS2's impact on the p53 signaling pathway.
  • Low LASS2 expression correlated with advanced TNM stage in HCC and CCA.
  • LASS2 stabilizes p53 by inhibiting MDM2/MDMX-mediated degradation and promoting p53 phosphorylation and acetylation.

Conclusions:

  • LASS2 suppresses tumor growth in liver cancer through a p53-dependent mechanism.
  • LASS2 interacts with MDM2/MDMX to regulate p53 stability and activity.
  • LASS2 represents a promising therapeutic target for liver cancer treatment.

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