Related Experiment Video
Updated: Aug 5, 2025
Author Spotlight: Exploring Salidroside's Molecular Mechanisms in Breast Cancer Treatment
Published on: June 9, 2023
STX5 Inhibits Hepatocellular Carcinoma Adhesion and Promotes Metastasis by Regulating the PI3K/mTOR Pathway
Bin Zhang1,2, Ziyin Zhao2, Youpeng Wang3
1Key Laboratory of Marine Drugs, Ministry of Education School of Medicine & Pharmacy, Ocean University of China, Qingdao, Shandong, China.
Background And Aims:
Syntaxin 5 (STX5) is a member of the syntaxin or target-soluble SNAP receptor (t-SNARE) family and plays a critical role in autophagy. However, its function and molecular mechanism in tumor cell migration are still unknown. The role of STX5 in influencing hepatocellular carcinoma (HCC) is an important topic in our research.
Methods:
By using quantitative reverse transcription polymerase chain reaction (qPCR), western blotting, and immunohistochemical analysis of RNA and protein in tissues, we comprehensively evaluated data sets from public databases and clinical patient cohorts for STX5. The correlation of STX5 expression with the clinicopathological characteristics of HCC patients were assessed. In addition, we predicted signal pathways from differentially expressed genes (DEGs) and the Cancer Genome Atlas (TCGA) databases, and confirmed the prediction using integrated transcriptome and RNA-seq. We further investigated the underlying mechanisms of STX5 in the migration and adhesion of HCC cells both in vitro and in vivo.
Results:
In the TCGA dataset and our patient cohort, STX5 levels were significantly higher in HCC tissues than in adjacent normal liver tissues. At the same time, high expression of STX5 predicted worse prognosis in patients with liver cancer. High expression of STX5 indicates the decrease of adhesion and the increase of migration of HCC cells, and the conversion of epithelial-mesenchymal transition (EMT) in vitro via PI3K/mTOR pathway activation. Conversely, when Sirolimus, a phosphoinositide 3-kinase (PI3K)/AKT/mechanistic target of rapamycin (mTOR) inhibitor acts on cells simultaneously, STX5 overexpression-mediated enhancement of HCC metastasis is reversed. Double-negative regulation of STX5 and mTOR further enhanced the inhibitory effect of STX5 on HCC metastasis. In vivo, STX5 knockdown inhibited the metastasis of HCC cells.
Conclusions:
Our study demonstrates a novel research result that STX5 promotes HCC metastasis through PI3K/mTOR pathway. We believe that combined inhibition of STX5 and mTOR is a potential treatment for effectively prolonging patient survival and inhibiting HCC metastasis.
Insights
Syntaxin 5 (STX5) promotes hepatocellular carcinoma (HCC) metastasis by activating the PI3K/mTOR pathway. Combined inhibition of STX5 and mTOR offers a potential therapeutic strategy to improve patient survival and reduce HCC spread.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- Syntaxin 5 (STX5), a t-SNARE family member, is crucial for autophagy.
- The role of STX5 in hepatocellular carcinoma (HCC) cell migration and its underlying mechanisms remain largely unexplored.
Purpose of the Study:
- To investigate the function and molecular mechanism of STX5 in HCC cell migration.
- To evaluate the correlation between STX5 expression and HCC patient prognosis.
Main Methods:
- Quantitative reverse transcription polymerase chain reaction (qPCR), western blotting, and immunohistochemistry were used to analyze STX5 expression in public databases and clinical HCC cohorts.
- In vitro and in vivo experiments assessed the impact of STX5 on HCC cell migration, adhesion, and epithelial-mesenchymal transition (EMT).
- Signal pathway analysis utilized TCGA and integrated transcriptome/RNA-seq data.
Main Results:
- STX5 expression was significantly elevated in HCC tissues compared to normal liver tissues, correlating with worse patient prognosis.
- Overexpression of STX5 enhanced HCC cell migration and EMT in vitro via PI3K/mTOR pathway activation.
- STX5 knockdown inhibited HCC metastasis in vivo, and combined inhibition of STX5 and mTOR reversed STX5-induced metastasis.
Conclusions:
- STX5 promotes HCC metastasis through the PI3K/mTOR signaling pathway.
- Combined inhibition of STX5 and mTOR represents a promising therapeutic approach for HCC treatment.
- Targeting STX5 and mTOR may improve survival rates and inhibit metastasis in HCC patients.
More Related Videos
09:29Development and Maintenance of a Preclinical Patient Derived Tumor Xenograft Model for the Investigation of Novel Anti-Cancer Therapies
Published on: September 30, 2016
08:50In Vitro Cultivation Techniques for Modeling Liver Organogenesis, Building Assembloids, and Designing Synthetic Tissues using Human Cell Lines
Published on: April 18, 2025
Related Concept Videos
01:22PI3K/mTOR/AKT Signaling Pathway
03:03mTOR Signaling and Cancer Progression
The mTOR pathway or the...
01:20The JAK-STAT Signaling Pathway
02:30Metastasis
Epithelial-to-Mesenchymal Transition
The epithelial-to-mesenchymal transition or EMT is a developmental process commonly observed in wound healing, embryogenesis, and cancer metastasis. EMT is induced by transforming growth factor-beta (TGF-β) or receptor tyrosine kinase (RTK) ligands, which further...
01:24Regulation of Angiogenesis and Blood Supply
01:17Intracellular Signaling Affects Focal Adhesions
Some...