Single-cell and multi-omics integration reveals cholesterol biosynthesis as a synergistic target with HER2 in aggressive breast cancer
Breast cancer stands as one of the most prevalent malignancies affecting women. Alterations in molecular pathways in cancer cells represent key regulatory disruptions that drive malignancy, influencing cancer cell survival, proliferation, and potentially modulating therapeutic responsiveness. Theref...
Saved in:
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2025-01-01
|
| Series: | Computational and Structural Biotechnology Journal |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2001037025001540 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849316071515881472 |
|---|---|
| author | Tzu-Yang Tseng Chiao-Hui Hsieh Jie-Yu Liu Hsuan-Cheng Huang Hsueh-Fen Juan |
| author_facet | Tzu-Yang Tseng Chiao-Hui Hsieh Jie-Yu Liu Hsuan-Cheng Huang Hsueh-Fen Juan |
| author_sort | Tzu-Yang Tseng |
| collection | DOAJ |
| description | Breast cancer stands as one of the most prevalent malignancies affecting women. Alterations in molecular pathways in cancer cells represent key regulatory disruptions that drive malignancy, influencing cancer cell survival, proliferation, and potentially modulating therapeutic responsiveness. Therefore, decoding the intricate molecular mechanisms and identifying novel therapeutic targets through systematic computational approaches are essential steps toward advancing effective breast cancer treatments. In this study, we developed an integrative computational framework that combines single-cell RNA sequencing (scRNA-seq) and multi-omics analyses to delineate the functional characteristics of malignant cell subsets in breast cancer patients. Our analyses revealed a significant correlation between cholesterol biosynthesis and HER2 expression in malignant breast cancer cells, supported by proteomics data, gene expression profiles, drug treatment scores, and cell-surface HER2 intensity measurements. Given previous evidence linking cholesterol biosynthesis to HER2 membrane dynamics, we proposed a combinatorial strategy targeting both pathways. Experimental validation through clonogenic and viability assays demonstrated that simultaneous inhibition of cholesterol biosynthesis (via statins) and HER2 (via Neratinib) synergistically reduced malignant breast cancer cells, even in HER2-negative contexts. Through systematic analysis of scRNA-seq and multi-omics data, our study computationally identified and experimentally validated cholesterol biosynthesis and HER2 as novel combinatorial therapeutic targets in breast cancer. This data-driven approach highlights the potential of leveraging multiple molecular profiling techniques to uncover previously unexplored treatment strategies. |
| format | Article |
| id | doaj-art-a935409594194b32b7ffc6a8aef6b1af |
| institution | Kabale University |
| issn | 2001-0370 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Computational and Structural Biotechnology Journal |
| spelling | doaj-art-a935409594194b32b7ffc6a8aef6b1af2025-08-20T03:51:58ZengElsevierComputational and Structural Biotechnology Journal2001-03702025-01-01271719173110.1016/j.csbj.2025.04.030Single-cell and multi-omics integration reveals cholesterol biosynthesis as a synergistic target with HER2 in aggressive breast cancerTzu-Yang Tseng0Chiao-Hui Hsieh1Jie-Yu Liu2Hsuan-Cheng Huang3Hsueh-Fen Juan4Department of Life Science, National Taiwan University, Taipei, TaiwanDepartment of Life Science, National Taiwan University, Taipei, TaiwanDepartment of Life Science, National Taiwan University, Taipei, TaiwanInstitute of Biomedical Informatics, National Yang Ming Chiao Tung University, Taipei, Taiwan; Correspondence to: Institute of Biomedical Informatics, National Yang Ming Chiao Tung University, No.155, Sec.2, Linong Street, Taipei 112, Taiwan.Department of Life Science, National Taiwan University, Taipei, Taiwan; Graduate Institute of Biomedical Electronics and Bioinformatics, National Taiwan University, Taipei, Taiwan; Center for Computational and Systems Biology, National Taiwan University, Taipei, Taiwan; Center for Advanced Computing and Imaging in Biomedicine, National Taiwan University, Taipei, Taiwan; Correspondence to: Department of Life Science, Graduate Institute of Biomedical Electronics andBioinformatics, Center for Computational and Systems Biology, National Taiwan University, No. 1, Sec. 4,Roosevelt Road, Taipei 106, Taiwan.Breast cancer stands as one of the most prevalent malignancies affecting women. Alterations in molecular pathways in cancer cells represent key regulatory disruptions that drive malignancy, influencing cancer cell survival, proliferation, and potentially modulating therapeutic responsiveness. Therefore, decoding the intricate molecular mechanisms and identifying novel therapeutic targets through systematic computational approaches are essential steps toward advancing effective breast cancer treatments. In this study, we developed an integrative computational framework that combines single-cell RNA sequencing (scRNA-seq) and multi-omics analyses to delineate the functional characteristics of malignant cell subsets in breast cancer patients. Our analyses revealed a significant correlation between cholesterol biosynthesis and HER2 expression in malignant breast cancer cells, supported by proteomics data, gene expression profiles, drug treatment scores, and cell-surface HER2 intensity measurements. Given previous evidence linking cholesterol biosynthesis to HER2 membrane dynamics, we proposed a combinatorial strategy targeting both pathways. Experimental validation through clonogenic and viability assays demonstrated that simultaneous inhibition of cholesterol biosynthesis (via statins) and HER2 (via Neratinib) synergistically reduced malignant breast cancer cells, even in HER2-negative contexts. Through systematic analysis of scRNA-seq and multi-omics data, our study computationally identified and experimentally validated cholesterol biosynthesis and HER2 as novel combinatorial therapeutic targets in breast cancer. This data-driven approach highlights the potential of leveraging multiple molecular profiling techniques to uncover previously unexplored treatment strategies.http://www.sciencedirect.com/science/article/pii/S2001037025001540Single-cell RNA sequencingCombinatorial therapeutic targetsCholesterol biosynthesisBreast cancer |
| spellingShingle | Tzu-Yang Tseng Chiao-Hui Hsieh Jie-Yu Liu Hsuan-Cheng Huang Hsueh-Fen Juan Single-cell and multi-omics integration reveals cholesterol biosynthesis as a synergistic target with HER2 in aggressive breast cancer Computational and Structural Biotechnology Journal Single-cell RNA sequencing Combinatorial therapeutic targets Cholesterol biosynthesis Breast cancer |
| title | Single-cell and multi-omics integration reveals cholesterol biosynthesis as a synergistic target with HER2 in aggressive breast cancer |
| title_full | Single-cell and multi-omics integration reveals cholesterol biosynthesis as a synergistic target with HER2 in aggressive breast cancer |
| title_fullStr | Single-cell and multi-omics integration reveals cholesterol biosynthesis as a synergistic target with HER2 in aggressive breast cancer |
| title_full_unstemmed | Single-cell and multi-omics integration reveals cholesterol biosynthesis as a synergistic target with HER2 in aggressive breast cancer |
| title_short | Single-cell and multi-omics integration reveals cholesterol biosynthesis as a synergistic target with HER2 in aggressive breast cancer |
| title_sort | single cell and multi omics integration reveals cholesterol biosynthesis as a synergistic target with her2 in aggressive breast cancer |
| topic | Single-cell RNA sequencing Combinatorial therapeutic targets Cholesterol biosynthesis Breast cancer |
| url | http://www.sciencedirect.com/science/article/pii/S2001037025001540 |
| work_keys_str_mv | AT tzuyangtseng singlecellandmultiomicsintegrationrevealscholesterolbiosynthesisasasynergistictargetwithher2inaggressivebreastcancer AT chiaohuihsieh singlecellandmultiomicsintegrationrevealscholesterolbiosynthesisasasynergistictargetwithher2inaggressivebreastcancer AT jieyuliu singlecellandmultiomicsintegrationrevealscholesterolbiosynthesisasasynergistictargetwithher2inaggressivebreastcancer AT hsuanchenghuang singlecellandmultiomicsintegrationrevealscholesterolbiosynthesisasasynergistictargetwithher2inaggressivebreastcancer AT hsuehfenjuan singlecellandmultiomicsintegrationrevealscholesterolbiosynthesisasasynergistictargetwithher2inaggressivebreastcancer |