ArticleThe Journal of clinical investigation2019
Cullin5 deficiency promotes small-cell lung cancer metastasis by stabilizing integrin β1.
Article in The Journal of clinical investigation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.
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Who cites it
62 citing papers in PubMed, 102 citations in OpenAlex.
- Post-translational modifications of integrins: molecular mechanisms and pathological implications.Cellular and molecular life sciences : CMLS · 2026Review
- CUL5-mediated ubiquitination in cancer cell therapy: context-dependent roles, molecular networks, and emerging therapeutic avenues.Frontiers in medicine · 2026Review
- Cul5: immune cell function and therapeutic potential.Frontiers in immunology · 2026Review
- The Crosstalk Between CRL5 and APC/C E3 Ligases Regulates Metastasis and Chemosensitivity of Cancer Cells.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Advancing small cell lung cancer metastasis research: innovations in preclinical mouse models.Cancer metastasis reviews · 2025Review
- The E3 ubiquitin ligase Cul5 regulates hematopoietic stem cell function for steady-state hematopoiesis in mice.The Journal of clinical investigation · 2025Article
- Nucleus-translocated glucokinase functions as a protein kinase to phosphorylate TAZ and promote tumour growth.Nature communications · 2025Article
- ITGA5 induces mesenchymal transformation to promote gliomas progression via PI3K/AKT/mTORC1 signaling pathway.Scientific reports · 2025Article
- High matrix stiffness accelerates migration of hepatocellular carcinoma cells through the integrin β1-Plectin-F-actin axis.BMC biology · 2025Article
- Periostin-mediated NOTCH1 activation between tumor cells and HSCs crosstalk promotes liver metastasis of small cell lung cancer.Journal of experimental & clinical cancer research : CR · 2025Article
- Small cell lung cancer with liver metastases: from underlying mechanisms to treatment strategies.Cancer metastasis reviews · 2024Review
- DCAF13 promotes ovarian cancer progression by activating FRAS1-mediated FAK signaling pathway.Cellular and molecular life sciences : CMLS · 2024Article
- Activating Invasion and Metastasis in Small Cell Lung Cancer: Role of the Tumour Immune Microenvironment and Mechanisms of Vasculogenesis, Epithelial-Mesenchymal Transition, Cell Migration, and Organ Tropism.Cancer reports (Hoboken, N.J.) · 2024Review
- [Research Progress on the Mechanism and Diagnostic Markers of Bone Metastasis in Small Cell Lung Cancer].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2024Review
- Therapeutic targeting ERRγ suppresses metastasis via extracellular matrix remodeling in small cell lung cancer.EMBO molecular medicine · 2024Article
- Integrating integrins with the hallmarks of cancer.Matrix biology : journal of the International Society for Matrix Biology · 2024Review
- Landscape and Treatment Options of Shapeshifting Small Cell Lung Cancer.Journal of clinical medicine · 2024Review
- FAK-LINC01089 negative regulatory loop controls chemoresistance and progression of small cell lung cancer.Oncogene · 2024Article
- Cullin5 drives experimental asthma exacerbations by modulating alveolar macrophage antiviral immunity.Nature communications · 2024Article
- FTO facilitates cancer metastasis by modifying the mCell communication and signaling : CCS · 2023Article
2 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
23 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Metastasis is the dominant cause of patient death in small-cell lung cancer (SCLC), and a better understanding of the molecular mechanisms underlying SCLC metastasis may potentially improve clinical treatment. Through genome-scale screening for key regulators of mouse Rb1-/- Trp53-/- SCLC metastasis using the pooled CRISPR/Cas9 library, we identified Cullin5 (CUL5) and suppressor of cytokine signaling 3 (SOCS3), two components of the Cullin-RING E3 ubiquitin ligase complex, as top candidates. Mechanistically, the deficiency of CUL5 or SOCS3 disrupted the functional formation of the E3 ligase complex and prevented the degradation of integrin β1, which stabilized integrin β1 and activated downstream focal adhesion kinase/SRC (FAK/SRC) signaling and eventually drove SCLC metastasis. Low expression levels of CUL5 and SOCS3 were significantly associated with high integrin β1 levels and poor prognosis in a large cohort of 128 clinical patients with SCLC. Moreover, the CUL5-deficient SCLCs were vulnerable to the treatment of the FDA-approved SRC inhibitor dasatinib. Collectively, this work identifies the essential role of CUL5- and SOCS3-mediated integrin β1 turnover in controlling SCLC metastasis, which might have therapeutic implications.
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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.