AP1S3 Promotes Proliferation and Invasion of Cholangiocarcinoma Cells and Modulates HER2 Trafficking
- 1Department of General Surgery, The Second Xiangya Hospital, Central South University, Changsha 410000, China
Abstract
Background: Cholangiocarcinoma (CCA) is an inflammation-associated malignancy with limited benefit from HER2-targeted therapy. Whether psoriasis is causally linked to CCA and how AP1S3 contributes remain unclear. Methods: We performed exploratory two-sample Mendelian randomization (MR), integrated bulk and single-cell transcriptomes, and used CCA cell lines and xenografts to examine AP1S3 and HER2 trafficking. Results: Strict MR (8 IVs; MHC excluded) gave an OR of 1.00 (95% CI 0.83–1.21; p = 0.98); the relaxed-threshold estimate (OR 1.12, 1.01–1.25; p = 0.037) was not robust (independent OR 1.05, 0.96–1.14; p = 0.30). IL-17A/TNF-α increased AP1S3 in CCA cells and activated NF-κB/RELA, but direct RELA binding was not demonstrated. AP1S3 was associated with a SCEL+ squamous-like program. AP1S3 co-precipitated with HER2 via EIPDLL (residues 930–935, kinase domain) and modulated HER2 trafficking; direct binding, isoform specificity and active recycling were not established. Conclusions The psoriasis–CCA association is inconclusive. AP1S3 is a candidate inflammatory regulator of HER2 trafficking and requires direct binding, loss-of-function and clinical validation.
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BibTeX
@article{shen2026ap1s3,
title = {{AP1S3 Promotes Proliferation and Invasion of Cholangiocarcinoma Cells and Modulates HER2 Trafficking}},
author = {Chen Shen and Ronglin Xu and Hui Zhou and Yongxiang Wang and Zhongtao Liu and Yang Xin and Tiantian Wang and Heng Zou and Zijian Zhang and Yu Wen},
journal = {Cells},
year = {2026},
month = nov,
doi = {10.3390/cells15212039},
url = {https://www.mdpi.com/2073-4409/15/21/2039},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - AP1S3 Promotes Proliferation and Invasion of Cholangiocarcinoma Cells and Modulates HER2 Trafficking
AU - Chen Shen
AU - Ronglin Xu
AU - Hui Zhou
AU - Yongxiang Wang
AU - Zhongtao Liu
AU - Yang Xin
AU - Tiantian Wang
AU - Heng Zou
AU - Zijian Zhang
AU - Yu Wen
PY - 2026
DA - 2026/11/09
JO - Cells
DO - 10.3390/cells15212039
UR - https://www.mdpi.com/2073-4409/15/21/2039
AB - Background: Cholangiocarcinoma (CCA) is an inflammation-associated malignancy with limited benefit from HER2-targeted therapy. Whether psoriasis is causally linked to CCA and how AP1S3 contributes remain unclear. Methods: We performed exploratory two-sample Mendelian randomization (MR), integrated bulk and single-cell transcriptomes, and used CCA cell lines and xenografts to examine AP1S3 and HER2 trafficking. Results: Strict MR (8 IVs; MHC excluded) gave an OR of 1.00 (95% CI 0.83–1.21; p = 0.98); the relaxed-threshold estimate (OR 1.12, 1.01–1.25; p = 0.037) was not robust (independent OR 1.05, 0.96–1.14; p = 0.30). IL-17A/TNF-α increased AP1S3 in CCA cells and activated NF-κB/RELA, but direct RELA binding was not demonstrated. AP1S3 was associated with a SCEL+ squamous-like program. AP1S3 co-precipitated with HER2 via EIPDLL (residues 930–935, kinase domain) and modulated HER2 trafficking; direct binding, isoform specificity and active recycling were not established. Conclusions The psoriasis–CCA association is inconclusive. AP1S3 is a candidate inflammatory regulator of HER2 trafficking and requires direct binding, loss-of-function and clinical validation.
SN - 2073-4409
ER -