Emerging evidence suggests that the sterile alpha-motif (SAM) and histidine-aspartate (HD) domain-containing protein 1 (SAMHD1) is implicated in various cancers, including hepatocellular carcinoma (HCC). However, its precise role in tumor cells and the underlying mechanisms remain unclear. This study aimed to investigate the expression patterns, prognostic values, and functional role of SAMHD1 in HCC progression. We constructed liver tissue microarrays using tumor and paired paratumor tissue specimens from 187 patients with primary HCC. Our findings indicate that nuclear SAMHD1 protein levels are increased in tumors compared to paratumor tissues. Moreover, nuclear SAMHD1 levels decline in advanced tumor stages, with higher SAMHD1 nuclear staining correlating with favorable prognostic outcomes. Hepatocyte-specific SAMHD1 knockout mice, generated by crossing SAMHD1 mice with Alb-cre mice, showed accelerated tumor progression in a diethylnitrosamine (DEN)-induced HCC model. In hepatoma cell lines, nuclear overexpression of SAMHD1 inhibited cell proliferation by stalling mitosis, independent of its deoxynucleotide triphosphohydrolase (dNTPase) function. Mechanistically, SAMHD1 interacts with the cohesin complex in nucleus, enhancing sister chromatid cohesion during cell division, which delays metaphase progression. Our findings suggest that nuclear SAMHD1 plays a critical role in slowing HCC progression by regulating mitosis, highlighting its potential as a therapeutic target by manipulating cohesin dynamics.

Download full-text PDF

Source
http://dx.doi.org/10.1002/advs.202411988DOI Listing

Publication Analysis

Top Keywords

hcc progression
12
nuclear samhd1
12
samhd1
11
nuclear overexpression
8
overexpression samhd1
8
cohesin complex
8
nuclear
6
hcc
6
progression
5
samhd1 induces
4

Similar Publications

Background: At present, the main clinical application of local ablation therapy, such as radiofrequency ablation (RFA), is to heat the tissue to a certain temperature. However, high temperature will cause thermal damage. Irreversible electroporation (IRE) is a novel minimally invasive local ablation technology for tumors.

View Article and Find Full Text PDF

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors, with the characteristics of high mortality and low 5-year survival rate. The potential role of BTF3 and PDCD2L in HCC remains unclear. Our study found that BTF3 expression was upregulated in hepatocellular carcinoma tissues, and its high expression was associated with poor prognosis.

View Article and Find Full Text PDF

Background: Hepatocellular carcinoma (HCC), considered as one of the most common and lethal cancers worldwide, has drawn significant attention from researchers.Extensively studied diverse cancers, the function of LIMA1 in tumorigenesis and cancer progression remains ambiguous..

View Article and Find Full Text PDF

ASPH dysregulates cell death and induces chemoresistance in hepatocellular carcinoma.

Cancer Lett

December 2024

Department of General Surgery, The Fourth Affiliated Hospital of Harbin Medical University, Harbin 150001, Heilongjiang Province, P.R. China. Electronic address:

Hepatocellular carcinoma (HCC) is resistant to multiple conventional drugs including sorafenib, leading to poor prognosis. Inducing cell death has been inextricably pursued in therapeutics, although targeted therapy and immunotherapy have made very limited progress. ASPH (Aspartate β-hydroxylase) can be breakthrough in meeting this unmet clinical need.

View Article and Find Full Text PDF

Synergistic Anticancer Strategy Targeting ECM Stiffness: Integration of Matrix Softening and Mechanical Signal Transduction Blockade in Primary Liver Cancers.

Adv Sci (Weinh)

December 2024

Zhejiang Key Laboratory of Multi-omics Precision Diagnosis and Treatment of Liver Diseases, Department of General Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310016, China.

The development of primary liver cancer (hepatocellular carcinoma [HCC] and intrahepatic cholangiocarcinoma [ICC]) is linked to its physical microenvironment, particularly extracellular matrix (ECM) stiffness. Potential anticancer strategies targeting ECM stiffness include prevention/reversal of the stiffening process and disruption of the response of cancer cells to mechanical signals from ECM. However, each strategy has limitations.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!