PUBLICATION
SHC adaptor protein 1 drives CAF-mediated immune exclusion and notch-dependent angiogenesis in lung adenocarcinoma
- Authors
- Wang, Z., Qiu, J., Yu, Y., Zhao, C., Dong, F., Liu, L., Ke, C., Yang, J., Lin, C.
- ID
- ZDB-PUB-251213-8
- Date
- 2025
- Source
- International journal of biological macromolecules : 149542 (Journal)
- Registered Authors
- Keywords
- LLPS, LUAD, SHC adaptor protein 1
- MeSH Terms
-
- Adenocarcinoma of Lung*/genetics
- Adenocarcinoma of Lung*/immunology
- Adenocarcinoma of Lung*/metabolism
- Adenocarcinoma of Lung*/pathology
- Angiogenesis
- Animals
- Cancer-Associated Fibroblasts*/immunology
- Cancer-Associated Fibroblasts*/metabolism
- Cancer-Associated Fibroblasts*/pathology
- Cell Line, Tumor
- Cell Movement
- Cell Proliferation
- Gene Expression Regulation, Neoplastic
- Humans
- Lung Neoplasms*/genetics
- Lung Neoplasms*/immunology
- Lung Neoplasms*/metabolism
- Lung Neoplasms*/pathology
- Neovascularization, Pathologic*/genetics
- Neovascularization, Pathologic*/metabolism
- Neovascularization, Pathologic*/pathology
- Receptors, Notch*/metabolism
- Signal Transduction
- Src Homology 2 Domain-Containing, Transforming Protein 1*/genetics
- Src Homology 2 Domain-Containing, Transforming Protein 1*/metabolism
- Tumor Microenvironment/genetics
- Tumor Microenvironment/immunology
- Zebrafish
- PubMed
- 41386608 Full text @ Int. J. Biol. Macromol.
Citation
Wang, Z., Qiu, J., Yu, Y., Zhao, C., Dong, F., Liu, L., Ke, C., Yang, J., Lin, C. (2025) SHC adaptor protein 1 drives CAF-mediated immune exclusion and notch-dependent angiogenesis in lung adenocarcinoma. International journal of biological macromolecules. :149542.
Abstract
Research shows that SHC Adaptor Protein 1 (SHC1) can undergo liquid-liquid phase separation (LLPS) in vitro. This study aims to explore the role of SHC1 in tumor angiogenesis and the tumor microenvironment in lung adenocarcinoma (LUAD). An optimal LLPS-risk signature was developed using 101 machine learning algorithm combinations. Functional enrichment, immune infiltration, and drug sensitivity analyses were performed to assess the biological and clinical relevance of the LLPS-risk signature. High-risk LUAD patients showed poorer prognosis, lower immune infiltration, and reduced response to immunotherapy. SHC1 expression was validated by single-cell transcriptomics and multiplex immunohistochemistry (mIHC). SHC1 was found to be a hub gene in the signature, associated with cancer-associated fibroblast (CAF) infiltration, tumor-derived endothelial cell (TEC) formation, and immune exclusion. SHC1 mediated vascular cell proliferation, migration, angiogenesis, and drug resistance in vitro. Zebrafish experiments confirmed SHC1's pro-angiogenic effects in vivo. RNA sequencing and Western blotting showed SHC1 regulates angiogenesis via the Notch pathway. This LLPS signature is a reliable biomarker for predicting survival and immunotherapy outcomes, with SHC1 as a key regulator of angiogenesis and the immune microenvironment.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping