ArticleOncotarget2016
Tumor suppressor Spred2 interaction with LC3 promotes autophagosome maturation and induces autophagy-dependent cell death.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 35 citations in OpenAlex.
- Poricoic Acid A attenuated TGF-β1-induced epithelial-mesenchymal transition in renal tubular epithelial cells through SPRY2/ERK signaling pathway.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2025Article
- Neurofibromin Encoded by theInternational journal of molecular sciences · 2025Article
- Loss of SPRED3 Causes Primary Hypothyroidism and Alters Thyroidal Expression of Autophagy Regulators LC3, p62, and ATG5 in Mice.International journal of molecular sciences · 2025Article
- SPRED2 Is a Novel Regulator of Autophagy in Hepatocellular Carcinoma Cells and Normal Hepatocytes.International journal of molecular sciences · 2024Article
- Autophagy in colitis-associated colon cancer: exploring its potential role in reducing initiation and preventing IBD-Related CAC development.Autophagy · 2024Review
- RREB1 regulates neuronal proteostasis and the microtubule network.Science advances · 2024Article
- Cancer incidence and surveillance strategies in individuals with RASopathies.American journal of medical genetics. Part C, Seminars in medical genetics · 2022Review
- SUFU suppresses ferroptosis sensitivity in breast cancer cells via Hippo/YAP pathway.iScience · 2022Article
- miR-140-3p regulates the osteogenic differentiation ability of bone marrow mesenchymal stem cells by targeting spred2-mediated autophagy.Molecular and cellular biochemistry · 2021Article
- MicroRNA-218 aggravates HExperimental and therapeutic medicine · 2021Article
- Thrombin aggravates hypoxia/reoxygenation injury of astrocytes by activating the autophagy pathway mediated by SPRED2.Experimental and therapeutic medicine · 2021Article
- Article
- Cav 1.3 damages the osteogenic differentiation in osteoporotic rats by negatively regulating Spred 2-mediated autophagy-induced cell senescence.Journal of cellular and molecular medicine · 2020Article
- The interaction mechanism between autophagy and apoptosis in colon cancer.Translational oncology · 2020Review
- The impact of the RASSF1C and PIWIL1 on DNA methylation: the identification of GMIP as a tumor suppressor.Oncotarget · 2020Article
- Progress in experimental research on SPRED protein family.The Journal of international medical research · 2020Review
- SASH1 suppresses triple-negative breast cancer cell invasion through YAP-ARHGAP42-actin axis.Oncogene · 2020Article
- Structure and Dynamics in the ATG8 Family From Experimental to Computational Techniques.Frontiers in cell and developmental biology · 2020Review
- The Nedd8-activating enzyme inhibitor MLN4924 suppresses colon cancer cell growthThe Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2018Article
- Ajuba inhibits hepatocellular carcinoma cell growth via targeting of β-catenin and YAP signaling and is regulated by E3 ligase Hakai through neddylation.Journal of experimental & clinical cancer research : CR · 2018Article
Corrections and comments
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Authors and funding
14 authors at 4 institutions in 2 countries.
Funding
Abstract
The tumor suppressor Spred2 (Sprouty-related EVH1 domain-2) induces cell death in a variety of cancers. However, the underlying mechanism remains to be elucidated. Here we show that Spred2 induces caspase-independent but autophagy-dependent cell death in human cervical carcinoma HeLa and lung cancer A549 cells. We demonstrate that ectopic Spred2 increased both the conversion of microtubule-associated protein 1 light chain 3 (LC3), GFP-LC3 puncta formation and p62/SQSTM1 degradation in A549 and HeLa cells. Conversely, knockdown of Spred2 in tumor cells inhibited upregulation of autophagosome maturation induced by the autophagy inducer Rapamycin, which could be reversed by the rescue Spred2. These data suggest that Spred2 promotes autophagy in tumor cells. Mechanistically, Spred2 co-localized and interacted with LC3 via the LC3-interacting region (LIR) motifs in its SPR domain. Mutations in the LIR motifs or deletion of the SPR domain impaired Spred2-mediated autophagosome maturation and tumor cell death, indicating that functional LIR is required for Spred2 to trigger tumor cell death. Additionally, Spred2 interacted and co-localized with p62/SQSTM1 through its SPR domain. Furthermore, the co-localization of Spred2, p62 and LAMP2 in HeLa cells indicates that p62 may be involved in Spred2-mediated autophagosome maturation. Inhibition of autophagy using the lysosomal inhibitor chloroquine, reduced Spred2-mediated HeLa cell death. Silencing the expression of autophagy-related genes ATG5, LC3 or p62 in HeLa and A549 cells gave similar results, suggesting that autophagy is required for Spred2-induced tumor cell death. Collectively, these data indicate that Spred2 induces tumor cell death in an autophagy-dependent manner.
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Registered trials
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.