2. Academic Validation
  3. LASS2 enhances p53 protein stability and nuclear import to suppress liver cancer progression through interaction with MDM2/MDMX

LASS2 enhances p53 protein stability and nuclear import to suppress liver cancer progression through interaction with MDM2/MDMX

  • Cell Death Discov. 2023 Nov 14;9(1):414. doi: 10.1038/s41420-023-01709-2.
Qingqing Zhao # 1,  Wei He # 2 3,  Zhouheng Liu 2 3,  Liangliang Huang 4,  Xiaoli Yang 2 3,  Yong Liu 5 6,  Rui Chen 1,  Xun Min 7 8,  Yan Yang 9 10 11
Affiliations

Affiliations

  • 1 Department of General Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, China.
  • 2 Department of Laboratory Medicine, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, China.
  • 3 School of Laboratory Medicine, Zunyi Medical University, Zunyi, Guizhou, China.
  • 4 Department of General Surgery, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Pudong, Shanghai, China.
  • 5 School of Forensic Medicine, Zunyi Medical University, Zunyi, Guizhou, China.
  • 6 Center of Forensic Expertise, Affiliated hospital of Zunyi Medical University, Zunyi, Guizhou, China.
  • 7 Department of Laboratory Medicine, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, China. minxunzmu@163.com.
  • 8 School of Laboratory Medicine, Zunyi Medical University, Zunyi, Guizhou, China. minxunzmu@163.com.
  • 9 Department of Laboratory Medicine, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, China. yanyangzmu@163.com.
  • 10 School of Laboratory Medicine, Zunyi Medical University, Zunyi, Guizhou, China. yanyangzmu@163.com.
  • 11 School of Forensic Medicine, Zunyi Medical University, Zunyi, Guizhou, China. yanyangzmu@163.com.
  • # Contributed equally.
PMID: 37963859 DOI: 10.1038/s41420-023-01709-2
Abstract

LASS2 functions as a tumor suppressor in hepatocellular carcinoma (HCC), the most common type of primary liver Cancer, but the underlying mechanism of its action remains largely unknown. Moreover, details on its role and the downstream mechanisms in Cholangiocarcinoma (CCA) and hepatoblastoma (HB), are rarely reported. Herein, LASS2 overexpression was found to significantly inhibit proliferation, migration, invasion and induce Apoptosis in hepatoma cells with wild-type (HB cell line HepG2) and mutated p53 (HCC cell line HCCLM3 and CCA cell line HuCCT1). Gene set enrichment analysis determined the enrichment of the differentially expressed genes caused by LASS2 in the p53 signaling pathway. Moreover, the low expression of LASS2 in HCC and CCA tumor tissues was correlated with the advanced tumor-node-metastasis (TNM) stage, and the protein expression of LASS2 positively correlated with acetylated p53 (Lys373) protein levels. At least to some extent, LASS2 exerts its tumor-suppressive effects in a p53-dependent manner, in which LASS2 interacts with MDM2/MDMX and causes dual inhibition to disrupt p53 degradation by MDM2/MDMX. In addition, LASS2 induces p53 phosphorylation at ser15 and acetylation at lys373 to promote translocation from cytoplasm to nucleus. These findings provide new insights into the LASS2-induced tumor suppression mechanism in liver Cancer and suggest LASS2 could serve as a potential therapeutic target for liver Cancer.

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