---
title: "Dauriporphine Inhibits NSCLC Growth and Stemness by Targeting USP7/CASK Pathway"
id: "pubmed-42670798"
canonical_url: "https://medichelpline.com/clinical-feed/pubmed-42670798"
content_type: "clinical_feed_article"
specialty: "Oncology"
source_name: "PubMed / NCBI"
source_url: "https://pubmed.ncbi.nlm.nih.gov/42670798/"
doi: "10.1002/ddr.70373"
published_at: "2026-09-01T00:00:00.000Z"
evidence_level: "Journal Article"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Dauriporphine Inhibits NSCLC Growth and Stemness by Targeting USP7/CASK Pathway
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/pubmed-42670798
- **Specialty:** [Oncology](https://medichelpline.com/clinical-feed/oncology.md)
- **Primary Source:** PubMed / NCBI
- **Source URL:** [Original Journal Publication](https://pubmed.ncbi.nlm.nih.gov/42670798/)
- **DOI:** [10.1002/ddr.70373](https://doi.org/10.1002%2Fddr.70373)
- **Published At:** 2026-09-01T00:00:00.000Z
- **Evidence Rating:** Journal Article
## Executive GIST (TL;DR)
- Dauriporphine, an aporphine monomer from Menispermum dauricum DC, shows anti-cancer activity in **non-small cell lung cancer (NSCLC)**, reducing proliferation, invasion, migration, and stemness (all p < 0.05). - A range of in vitro assays were used: CCK-8 for viability, EdU for proliferation, flow cytometry for apoptosis, transwell for invasion, scratch assay for migration, and sphere formation for stemness. - Bioinformatics and weighted gene co-expression network analysis (WGCNA) identified **CASK** (calcium/calmodulin-dependent serine protein kinase) as a core molecular target associated with dauriporphine activity in NSCLC. - CASK expression was elevated in NSCLC clinical samples and cell lines (p < 0.05); reducing CASK correlated with the anti-cancer effects of dauriporphine (p < 0.05). - **USP7** (ubiquitin-specific protease 7) was shown to interact with and stabilize CASK by deubiquitination (p < 0.05); silencing USP7 decreased proliferation, metastasis, and stemness through inhibition of CASK (p < 0.05). - Dauriporphine physically interacted with USP7; forced USP7 overexpression reversed dauriporphine’s inhibitory effects on malignant phenotypes (p < 0.05), implicating USP7 as a functional target. - In vivo xenograft experiments demonstrated that dauriporphine reduced tumor growth and lowered USP7 and CASK expression in tumors (p < 0.05). - Mechanistic conclusion: dauriporphine promotes proteasomal degradation of CASK by inhibiting **USP7**-mediated deubiquitination, thereby blocking key malignant phenotypes in NSCLC cells. - The study proposes USP7 and CASK as potential molecular targets for dauriporphine-based therapeutic strategies in NSCLC. - Detailed experimental parameters, sample sizes, and specific quantitative results beyond reported significance values were not provided in the abstract and therefore are not reported here.
## Clinical Analysis & Structured Key Points
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Affiliations Expand ### Affiliation * 1 Department of Traditional Chinese Medicine, Shanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University, Taiyuan, Shanxi, China. * PMID: **42670798** * DOI: [ 10.1002/ddr.70373 ](https://doi.org/10.1002/ddr.70373) Item in Clipboard # Dauriporphine Suppresses Cell Proliferation, Metastasis, and Stemness of Non-Small Cell Lung Cancer Through the Regulation of the USP7/CASK Pengxiao Hou et al. Drug Dev Res. 2026 Sep. Show details Display options Display options Format Abstract PubMed PMID Drug Dev Res Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Drug+Dev+Res%22%5Bjour%5D&sort=date&sort_order=desc) * [ Search in NLM Catalog ](https://www.ncbi.nlm.nih.gov/nlmcatalog?term=%22Drug+Dev+Res%22%5BTitle+Abbreviation%5D) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42670798/) . 2026 Sep;87(6):e70373. doi: 10.1002/ddr.70373. ### Authors [Pengxiao Hou](https://pubmed.ncbi.nlm.nih.gov/?term=Hou+P&cauthor_id=42670798)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42670798/#short-view-affiliation-1 "Department of Traditional Chinese Medicine, Shanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University, Taiyuan, Shanxi, China."), [Qian Wu](https://pubmed.ncbi.nlm.nih.gov/?term=Wu+Q&cauthor_id=42670798)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42670798/#short-view-affiliation-1 "Department of Traditional Chinese Medicine, Shanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University, Taiyuan, Shanxi, China.") ### Affiliation * 1 Department of Traditional Chinese Medicine, Shanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University, Taiyuan, Shanxi, China. * PMID: **42670798** * DOI: [ 10.1002/ddr.70373 ](https://doi.org/10.1002/ddr.70373) Item in Clipboard Cite Display options Display options Format Abstract PubMed PMID ## Abstract Dauriporphine is a monomer extracted from Menispermum dauricum DC, and it exhibits anti-cancer effect in non-small cell lung cancer (NSCLC). The regulatory mechanism of dauriporphine remains incompletely understood, and this study focused on its molecular targets in NSCLC progression. Cell viability, proliferation, apoptosis, invasion, migration, and stemness were evaluated using cell counting kit-8, ethynyl-2'-deoxyuridine assay, flow cytometry, transwell assay, scratch assay, and sphere formation assay, respectively. Bioinformatics analysis and weighted gene co-expression network analysis (WGCNA) were performed to identify targets of dauriporphine in NSCLC. The mRNA and protein expression was quantified using qPCR and Western blot. Co-immunoprecipitation was used to analyze protein interaction and ubiquitination regulation between ubiquitin-specific protease 7 (USP7) and calcium/calmodulin-dependent serine protein kinase (CASK). The role of dauriporphine in vivo was explored using xenograft tumor model. Dauriporphine restrained proliferation, invasion, migration, and stemness of NSCLC cells (p < 0.05). Bioinformatics analysis and WGCNA identified CASK as a core target of dauriporphine in NSCLC. CASK was highly up-regulated in NSCLC samples and cells (p < 0.05). Anti-cancer effects of dauriporphine on NSCLC cells were associated with reduced CASK expression (p < 0.05). USP7 stabilized CASK protein by inducing deubiquitination (p < 0.05). Silencing USP7 restrained NSCLC cell proliferation, metastasis, and stemness by inhibiting CASK (p < 0.05). Dauriporphine interacted with USP7, and then USP7 overexpression reversed the inhibition of dauriporphine in NSCLC cell malignant behaviors (p < 0.05). Dauriporphine reduced tumor growth in vivo and down-regulated USP7 and CASK expression (p < 0.05). This study suggested that dauriporphine blocked the key malignant phenotypes of NSCLC cells via inhibiting USP7-mediated deubiquitination of CASK, thereby promoting its proteasomal degradation. The study elucidates a molecular mechanism underlying anti-tumor role of dauriporphine and providing potential targets for dauriporphine treatment. **Keywords:** calcium/calmodulin‐dependent serine protein kinase; dauriporphine; non‐small cell lung cancer; ubiquitin‐specific protease 7. © 2026 Wiley Periodicals LLC. [PubMed Disclaimer](https://pubmed.ncbi.nlm.nih.gov/disclaimer/) ## Similar articles * [ USP7 Stabilizes MESP1 To Promote the Malignant Progression of Non-Small Cell Lung Cancer. ](https://pubmed.ncbi.nlm.nih.gov/41563568/) Jiang S, Rong L, Yi F, Yang P, Yang L.Jiang S, et al.Appl Biochem Biotechnol. 2026 Apr;198(4):2623-2638. doi: 10.1007/s12010-025-05510-y. Epub 2026 Jan 21.Appl Biochem Biotechnol. 2026.PMID: 41563568 * [ Study on the regulatory mechanism of luteolin inhibiting WDR72 on the proliferation and metastasis of non small cell lung cancer. ](https://pubmed.ncbi.nlm.nih.gov/40216870/) Shi G, Wei J, Rahemu S, Zhou J, Li X.Shi G, et al.Sci Rep. 2025 Apr 11;15(1):12398. doi: 10.1038/s41598-025-96666-4.Sci Rep. 2025.PMID: 40216870Free PMC article. * [ β-hydroxybutyrate, a ketone body, suppresses tumor growth, stemness, and invasive phenotypes in non-small cell lung cancer. ](https://pubmed.ncbi.nlm.nih.gov/40545696/) Huang Y, Ding J, Zhu Y, Shi J, Liu R, Wu C, Han L, Zhang M.Huang Y, et al.Cancer Biol Ther. 2025 Dec;26(1):2516825. doi: 10.1080/15384047.2025.2516825. Epub 2025 Jun 22.Cancer Biol Ther. 2025.PMID: 40545696Free PMC article. * [ LAPTM4B promotes gefitinib resistance and tumor stemness in non-small cell lung cancer by stabilizing RPS3 through inhibiting its ubiquitination. ](https://pubmed.ncbi.nlm.nih.gov/42612828/) Jiang Y, Xie WJ, Chen RW, Huang CL, You WQ, Chen H, You WW, Chen WX, Xu S, Xu JP.Jiang Y, et al.Biochim Biophys Acta Mol Cell Res. 2026 Oct;1873(7):120212. doi: 10.1016/j.bbamcr.2026.120212. Epub 2026 Aug 18.Biochim Biophys Acta Mol Cell Res. 2026.PMID: 42612828 * [ Dauriporphine Inhibits the Proliferation, Migration, Angiogenesis, and Glycolysis in Lung Cancer Cells by Repressing PGK1 Expression via CEBPA. ](https://pubmed.ncbi.nlm.nih.gov/42390016/) Hou P, Liang Z, Wu Q.Hou P, et al.Biofactors. 2026 Jul-Aug;52(4):e70125. doi: 10.1002/biof.70125.Biofactors. 2026.PMID: 42390016Free PMC article. [ See all similar articles ](https://pubmed.ncbi.nlm.nih.gov/?linkname=pubmed_pubmed&from_uid=42670798) ## References 1. 1. Alduais, Y., H. Zhang, F. Fan, J. Chen, and B. Chen. 2023. “Non‐Small Cell Lung Cancer (NSCLC): A Review of Risk Factors, Diagnosis, and Treatment.” Medicine 102, no. 8: e32899. 2. 1. Chen, Y. M., W. Xu, Y. Liu, et al. 2023. “Anomanolide C Suppresses Tumor Progression and Metastasis by Ubiquitinating GPX4‐driven Autophagy‐Dependent Ferroptosis in Triple Negative Breast Cancer.” International Journal of Biological Sciences 19, no. 8: 2531–2550. 3. 1. Chu, X., W. Tian, J. Ning, et al. 2024. “Cancer Stem Cells: Advances in Knowledge and Implications for Cancer Therapy.” Signal Transduction and Targeted Therapy 9, no. 1: 170. 4. 1. Deng, B., X. L. Jiang, Z. B. Tan, et al. 2021. “Dauricine Inhibits Proliferation and Promotes Death of Melanoma Cells via Inhibition of Src/STAT3 Signaling.” Phytotherapy Research 35, no. 7: 3836–3847. 5. 1. Du, J., K. Yu, J. Zeng, et al. 2026. “Avicularin Induces Apoptosis in NSCLC by Promoting USP7‐mediated Degradation of FOXM1.” Naunyn‐Schmiedeberg's Archives of Pharmacology 399, no. 1: 1371–1380. 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