ArticleEBioMedicine2019
Loss of Scribble confers cisplatin resistance during NSCLC chemotherapy via Nox2/ROS and Nrf2/PD-L1 signaling.
Article in EBioMedicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 1 of them a synthesis that pooled it.
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Who cites it
31 citing papers in PubMed, 1 synthesis or guideline pooled it, 66 citations in OpenAlex.
- Prognostic and clinicopathological significance of NRF2 expression in non-small cell lung cancer: A meta-analysis.PloS one · 2020Pooled it
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- Mechanism of N6-methyladenosine (m6A)-mediated upregulation of LINC00958 in the growth of cervical cancer.Frontiers in oncology · 2026Article
- Silibinin Anticancer Effects Through the Modulation of the Tumor Immune Microenvironment in Triple-Negative Breast Cancer.International journal of molecular sciences · 2025Review
- Decoding the NRF2-NOTCH Crosstalk in Lung Cancer-An Update.Antioxidants (Basel, Switzerland) · 2025Review
- Article
- miRNA-199b-5p suppresses of oral squamous cell carcinoma by targeting apical-basolateral polarity via Scribble/Lgl.Molecular therapy. Nucleic acids · 2024Article
- Exploiting acquired vulnerability to develop novel treatments for cholangiocarcinoma.Cancer cell international · 2024Review
- Molecular basis, potential biomarkers, and future prospects of OSCC and PD-1/PD-L1 related immunotherapy methods.Heliyon · 2024Review
- Estrogen Regulates Scribble Localization in Endometrial Epithelial Cells Through Acyl Protein Thioesterase (APT)-Mediated S-Palmitoylation in Adenomyosis.Reproductive sciences (Thousand Oaks, Calif.) · 2024Article
- Cell polarity changes in cancer initiation and progression.The Journal of cell biology · 2024Review
- The Association between NADPH Oxidase 2 (NOX2) and Drug Resistance in Cancer.Current cancer drug targets · 2024Review
- TRIM17-mediated ubiquitination and degradation of RBM38 promotes cisplatin resistance in non-small cell lung cancer.Cellular oncology (Dordrecht, Netherlands) · 2023Article
- Formyl-peptide receptor 2 signalling triggers aerobic metabolism of glucose through Nox2-dependent modulation of pyruvate dehydrogenase activity.Open biology · 2023Article
- Article
- Redox Signaling Modulates Activity of Immune Checkpoint Inhibitors in Cancer Patients.Biomedicines · 2023Review
- miR-106a-5p carried by tumor-derived extracellular vesicles promotes the invasion and metastasis of ovarian cancer by targeting KLF6.Clinical & experimental metastasis · 2022Article
- LncRNA SNHG12 in extracellular vesicles derived from carcinoma-associated fibroblasts promotes cisplatin resistance in non-small cell lung cancer cells.Bioengineered · 2022Article
- Application and prospect of ROS-related nanomaterials for orthopaedic related diseases treatment.Frontiers in chemistry · 2022Review
- Aberrant ROS Served as an Acquired Vulnerability of Cisplatin-Resistant Lung Cancer.Oxidative medicine and cellular longevity · 2022Article
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundCisplatin resistance remains a major clinical obstacle to the successful treatment of non-small cell lung cancer (NSCLC). Scribble contributes to ROS-induced inflammation and cisplatin-elevated toxic reactive oxygen species (ROS) promotes cell death. However, it is unknown whether and how Scribble is involved in the cisplatin-related cell death and the underlying mechanism of Scribble in response to chemotherapies and in the process of oxidative stress in NSCLC.
methodsWe used two independent cohorts of NSCLC samples derived from patients treated with platinum-containing chemotherapy and xenograft modeling in vivo. We analyzed the correlation between Scribble and Nox2 or Nrf2/PD-L1 both in vivo and in vitro, and explored the role of Scribble in cisplatin-induced ROS and apoptosis.
findingsClinical analysis revealed that Scribble expression positively correlated with clinical outcomes and chemotherapeutic sensitivity in NSCLC patients. Scribble protected Nox2 protein from proteasomal degradation. Scribble knockdown induced cisplatin resistance by blocking Nox2/ROS and apoptosis in LRR domain-dependent manner. In addition, low levels of Scribble correlated with high levels of PD-L1 via activation of Nrf2 transcription in vivo and in vitro. INTERPRETATIONS: Our study revealed that polarity protein Scribble increased cisplatin-induced ROS generation and is beneficial to chemotherapeutic outcomes in NSCLC. Although Scribble deficiency tends to lead to cisplatin resistance by Nox2/ROS and Nrf2/PD-L1, it is still possible that Scribble deficiency-induced PD-L1 may yield benefits in immunotherapy. FUND: National Key R&D Program of China, Strategic Priority Research Program of the Chinese Academy of Sciences, National Natural Science Foundation of China, China Postdoctoral Science Foundation.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.