ArticleOncogene2017
Smurf1 regulates lung cancer cell growth and migration through interaction with and ubiquitination of PIPKIγ.
Article in Oncogene, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 57 citations in OpenAlex.
- SERHL regulates invasion and metastasis through KLF16-PLCB1/PRKCA signaling in gastric cancer cells.Genes & diseases · 2026Article
- PIPKIγ promotes non-homologous end joining through LIG4 to enhance radiotherapy resistance in triple-negative breast cancer.Cell death & disease · 2025Article
- Phosphoinositide kinases in cancer: from molecular mechanisms to therapeutic opportunities.Nature reviews. Cancer · 2025Review
- Expression of SMURF family in pancreatic cancer and its effect on cell proliferation and migration.Frontiers in oncology · 2025Article
- TC2N inhibits distant metastasis and stemness of breast cancer via blocking fatty acid synthesis.Journal of translational medicine · 2024Article
- Review
- Smurf1 regulates ameloblast polarization by ubiquitination-mediated degradation of RhoA.Cell proliferation · 2023Article
- PIP kinases: A versatile family that demands further therapeutic attention.Advances in biological regulation · 2023Article
- CRISPR-mediated MECOM depletion retards tumor growth by reducing cancer stem cell properties in lung squamous cell carcinoma.Molecular therapy : the journal of the American Society of Gene Therapy · 2022Article
- MHY4571, a novel diarylcyclohexanone derivative, exerts anti-cancer activity by regulating the PKA-cAMP-response element-binding protein pathway in squamous cell lung cancer.Experimental hematology & oncology · 2022Article
- Downregulation of NEDD4L by EGFR signaling promotes the development of lung adenocarcinoma.Journal of translational medicine · 2022Article
- Overexpressed Smurf1 is degraded in glioblastoma cells through autophagy in a p62-dependent manner.FEBS open bio · 2022Article
- Lactate increases tumor malignancy by promoting tumor small extracellular vesicles productionFrontiers in oncology · 2022Article
- Targeting type Iγ phosphatidylinositol phosphate kinase overcomes oxaliplatin resistance in colorectal cancer.Theranostics · 2022Article
- lncRNA FEZF1-AS1 regulates biological behaviors of cervical cancer by targeting miRNA-1254.Food science & nutrition · 2021Article
- SMURF1, a promoter of tumor cell progression?Cancer gene therapy · 2021Review
- Exploring the Roles of HERC2 and the NEDD4L HECT E3 Ubiquitin Ligase Subfamily in p53 Signaling and the DNA Damage Response.Frontiers in oncology · 2021Review
- Article
- Complex roles of cAMP-PKA-CREB signaling in cancer.Experimental hematology & oncology · 2020Review
- Oncogenic Smurf1 promotes PTEN wild-type glioblastoma growth by mediating PTEN ubiquitylation.Oncogene · 2020Article
Corrections and comments
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Authors and funding
12 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Type Iγ phosphatidylinositol phosphate kinase (PIPKIγ), a phospholipid kinase generating PIP2, is positively expressed in breast cancer tissues, which correlates intimately with the progression of patients. However, little is known about the expression level of PIPKIγ in patients with other cancer types as well as their underlying regulation mechanisms. Here, we report that PIPKIγ is highly expressed in lung cancer tissues and its expression level is critical for lung cancer cell proliferation, which may serve as a prognostic marker for lung cancer patients. Meanwhile, we show that E3 ubiquitin ligase Smurf1 directly interacts with PIPKIγ and targets PIPKIγ for ubiquitination and degradation in lung cancer cells. Also, we discover that Smurf1 directly binds to the kinase domain of PIPKIγ via its C2 domain while Lysine 255 in PIPKIγ acts as the major ubiquitin acceptor site for Smurf1. In addition, we demonstrate that the phosphorylation mimicking mutant of Smurf1, Smurf1 T306D, prevents PIPKIγi2 from ubiquitination and subsequent degradation similar to the effect of forskolin-potentiated cAMP formation, suggesting that Thr306 in Smurf1 is critical for its phosphorylation by PKA. Moreover, PKA-Smurf1-PIPKIγ signal transduction takes a significant part in lung cancer cell growth and in vivo tumorigenesis. Thus, we propose that the PKA-Smurf1-PIPKIγ pathway has an important role in pulmonary tumorigenesis and imposes substantial clinical impact on development of novel diagnostic markers and therapeutic targets for lung cancer treatment.
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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.