ArticleBritish journal of cancer2020
ASCL1-regulated DARPP-32 and t-DARPP stimulate small cell lung cancer growth and neuroendocrine tumour cell proliferation.
Article in British journal of cancer, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 34 citations in OpenAlex.
- Dopamine DCell death & disease · 2025Article
- Immunohistochemical characterization and potential prognostic relevance of dopamine signaling in canine pulmonary adenocarcinoma.Frontiers in veterinary science · 2025Article
- Radiation dermatitis in the hairless mouse model mimics human radiation dermatitis.Scientific reports · 2024Article
- Synchronous double primary small cell lung cancer and invasive ductal breast carcinoma: a case report.BMC pulmonary medicine · 2024Article
- cAMP-PKA/EPAC signaling and cancer: the interplay in tumor microenvironment.Journal of hematology & oncology · 2024Review
- Evaluation of t-DARPP Expression Alteration in Association with DDR1 Expression in Non-Small Cell Lung Cancer.Iranian biomedical journal · 2024Article
- Altered splicing machinery in lung carcinoids unveils NOVA1, PRPF8 and SRSF10 as novel candidates to understand tumor biology and expand biomarker discovery.Journal of translational medicine · 2023Article
- Unravelling transcriptomic complexity in breast cancer through modulation of DARPP-32 expression and signalling pathways.Scientific reports · 2023Article
- Identification of SNP markers for canine mammary gland tumours in females based on a genome-wide association study - preliminary results.Journal of veterinary research · 2023Article
- The uprise of RNA biology in neuroendocrine neoplasms: altered splicing and RNA species unveil translational opportunities.Reviews in endocrine & metabolic disorders · 2023Review
- IKKα promotes lung adenocarcinoma growth through ERK signaling activation via DARPP-32-mediated inhibition of PP1 activity.NPJ precision oncology · 2023Article
- [Study on the Biological Function of Abemecilib in Inhibiting the Proliferation, Invasion and Migration of Small Cell Lung Cancer with High c-Myc Expression].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2023Article
- NDR1 activates CD47 transcription by increasing protein stability and nuclear location of ASCL1 to enhance cancer stem cell properties and evasion of phagocytosis in small cell lung cancer.Medical oncology (Northwood, London, England) · 2022Article
- Archetype tasks link intratumoral heterogeneity to plasticity and cancer hallmarks in small cell lung cancer.Cell systems · 2022Article
- DARPP-32 promotes ERBB3-mediated resistance to molecular targeted therapy in EGFR-mutated lung adenocarcinoma.Oncogene · 2022Article
- Suppressing STAT3 activity protects the endothelial barrier from VEGF-mediated vascular permeability.Disease models & mechanisms · 2021Article
- PP1, PKA and DARPP-32 in breast cancer: A retrospective assessment of protein and mRNA expression.Journal of cellular and molecular medicine · 2021Article
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundSmall cell lung cancer (SCLC) is the most aggressive form of lung cancer, and new molecular insights are necessary for prognostic and therapeutic advances.
methodsDopamine and cAMP-regulated phosphoprotein, Mr 32000 (DARPP-32) and its N-terminally truncated splice variant, t-DARPP, were stably overexpressed or ablated in human DMS-53 and H1048 SCLC cells. Functional assays and immunoblotting were used to assess how DARPP-32 isoforms regulate SCLC cell growth, proliferation, and apoptosis. DARPP-32-modulated SCLC cells were orthotopically injected into the lungs of SCID mice to evaluate how DARPP-32 and t-DARPP regulate neuroendocrine tumour growth. Immunostaining for DARPP-32 proteins was performed in SCLC patient-derived specimens. Bioinformatics analysis and subsequent transcription assays were used to determine the mechanistic basis of DARPP-32-regulated SCLC growth.
resultsWe demonstrate in mice that DARPP-32 and t-DARPP promote SCLC growth through increased Akt/Erk-mediated proliferation and anti-apoptotic signalling. DARPP-32 isoforms are overexpressed in SCLC patient-derived tumour tissue, but undetectable in physiologically normal lung. Achaete-scute homologue 1 (ASCL1) transcriptionally activates DARPP-32 isoforms in human SCLC cells.
conclusionsWe reveal new regulatory mechanisms of SCLC oncogenesis that suggest DARPP-32 isoforms may represent a negative prognostic indicator for SCLC and serve as a potential target for the development of new therapies.
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