Related Experiment Video
Updated: Aug 6, 2026
Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells
Published on: October 27, 2020
Protective TGFβ2/SMAD3 axis identified by TWAS in papillary thyroid cancer
Qinnan Zhang1, Jiayu Tang2, Ju Yang3
1Department of Endocrinology, Fifth People's Hospital of Shanghai Fudan University , Shanghai, China.
Abstract:
Papillary thyroid carcinoma (PTC) is the most common endocrine malignancy. Although generally indolent, a subset shows aggressive behaviour. Furthermore, the genetic heterogeneity of PTC is not fully explained by known driver mutations, underscoring the need to identify additional susceptibility genes and regulatory mechanisms. To identify additional susceptibility genes and regulatory mechanisms, we integrated transcriptome-wide association studies (TWAS) with summary-data-based Mendelian randomisation (SMR), joint/conditional testing (JCT), and colocalisation analyses across multiple independent cohorts, followed by heterogeneity in dependent instruments (HEIDI) test. Gene prioritisation analyses consistently highlighted TGFB2 and SMAD3 as candidate susceptibility genes for PTC, with SMR supporting putative protective effects. Besides, GEPIA confirmed the positive correlation between TGFB2 and SMAD3 expression in TCGA-THCA. Functional experiments in TPC-1 cells showed that TGFβ2 treatment inhibited cell proliferation and migration, induced apoptosis, and resulted in G0/G1 cell-cycle arrest, accompanied by increased SMAD3 phosphorylation, suggesting activation of canonical TGFβ signalling. Collectively, these findings bridge population-based genetic inference with mechanistic validation and suggest convergent evidence supporting a tumour-suppressive role of the TGFβ2/SMAD3 axis in PTC.
Insights
This study identifies TGFB2 and SMAD3 as key genes in papillary thyroid carcinoma (PTC). These genes show a tumor-suppressive role, potentially offering new therapeutic targets for this common endocrine malignancy.
Area of Science:
- Genetics
- Molecular Biology
- Endocrinology
Background:
- Papillary thyroid carcinoma (PTC) is the most prevalent endocrine malignancy, often indolent but with a subset exhibiting aggressive behavior.
- The genetic basis of PTC heterogeneity requires further elucidation beyond known driver mutations, necessitating the identification of additional susceptibility genes and regulatory pathways.
Purpose of the Study:
- To identify novel susceptibility genes and regulatory mechanisms in papillary thyroid carcinoma.
- To investigate the role of the TGFB2/SMAD3 signaling pathway in PTC pathogenesis.
Main Methods:
- Integration of transcriptome-wide association studies (TWAS) with summary-data-based Mendelian randomization (SMR), joint/conditional testing (JCT), and colocalization analyses.
- Gene prioritization analyses, expression correlation analysis (GEPIA), and functional experiments in TPC-1 cells.
Main Results:
- TGFB2 and SMAD3 were consistently highlighted as candidate susceptibility genes for PTC, with SMR analysis suggesting protective effects.
- GEPIA confirmed a positive correlation between TGFB2 and SMAD3 expression in TCGA-THCA data.
- TGFβ2 treatment in TPC-1 cells inhibited proliferation and migration, induced apoptosis, and caused cell-cycle arrest, indicating activation of the canonical TGFβ signaling pathway via SMAD3 phosphorylation.
Conclusions:
- Convergent evidence from population-based genetic inference and mechanistic validation supports a tumor-suppressive role for the TGFB2/SMAD3 axis in PTC.
- These findings contribute to understanding PTC genetic heterogeneity and suggest potential therapeutic targets.
More Related Videos
11:06Live Cell Imaging of the TGF- β/Smad3 Signaling Pathway In Vitro and In Vivo Using an Adenovirus Reporter System
Published on: July 30, 2018
11:38Visualization and Quantification of TGFβ/BMP/SMAD Signaling under Different Fluid Shear Stress Conditions using Proximity-Ligation-Assay
Published on: September 14, 2021
