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Updated: Jul 11, 2025

Yeast As a Chassis for Developing Functional Assays to Study Human P53
Published on: August 4, 2019
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.
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.
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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