ArticleJournal of experimental & clinical cancer research : CR2017
TGF-β2 initiates autophagy via Smad and non-Smad pathway to promote glioma cells' invasion.
Article in Journal of experimental & clinical cancer research : CR, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 53 papers.
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Who cites it
53 citing papers in PubMed, 81 citations in OpenAlex.
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- Blue light attenuates TGF-β2-induced epithelial-mesenchymal transition in human lens epithelial cells via autophagy impairment.BMC ophthalmology · 2022Article
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- Translational landscape of glioblastoma immunotherapy for physicians: guiding clinical practice with basic scientific evidence.Journal of hematology & oncology · 2022Review
- Targeting TGF-β signal transduction for fibrosis and cancer therapy.Molecular cancer · 2022Review
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- Chaperone-Mediated Autophagy Controls Proteomic and Transcriptomic Pathways to Maintain Glioma Stem Cell Activity.Cancer research · 2022Article
- Review
- TGFβ2 is a Prognostic Biomarker for Gastric Cancer and is Associated With Methylation and Immunotherapy Responses.Frontiers in genetics · 2022Article
- PAK3 promotes the metastasis of hepatocellular carcinoma by regulating EMT process.Journal of Cancer · 2022Article
- A Novel Defined Necroptosis-Related miRNAs Signature for Predicting the Prognosis of Colon Cancer.International journal of general medicine · 2022Article
- The role of TGF-β2 in cartilage development and diseases.Bone & joint research · 2021Article
- Review
- Autophagy in tumour immunity and therapy.Nature reviews. Cancer · 2021Review
Corrections and comments
- Retraction · 2021-12-20Duplication of/in Image · Error in Image · · see aslo: https://pubpeer.com/publications/90272E5C7A7D00E99639DEBFEA8711
- Retracted
Authors and funding
8 authors at 1 institution in 2 countries.
Funding
Abstract
backgroundGlioblastoma multiforme (GBM) is characterized by lethal aggressiveness and patients with GBM are in urgent need for new therapeutic avenues to improve quality of life. Current studies on tumor invasion focused on roles of cytokines in tumor microenvironment and numerous evidence suggests that TGF-β2 is abundant in glioma microenvironment and vital for glioma invasion. Autopagy is also emerging as a critical factor in aggressive behaviors of cancer cells; however, the relationship between TGF-β2 and autophagy in glioma has been poorly understood.
methodsU251, T98 and U87 GBM cell lines as well as GBM cells from a primary human specimen were used in vitro and in vivo to evaluate the effect of TGF-β2 on autophagy. Western blot, qPCR, immunofluorescence and transmission-electron microscope were used to detect target molecular expression. Lentivirus and siRNA vehicle were introduced to establish cell lines, as well as mitotracker and seahorse experiment to study the metabolic process in glioma. Preclinical therapeutic efficacy was evaluated in orthotopic xenograft mouse models.
resultsHere we demonstrated that TGF-β2 activated autophagy in human glioma cell lines and knockdown of Smad2 or inhibition of c-Jun NH2-terminal kinase, attenuated TGF-β2-induced autophagy. TGF-β2-induced autophagy is important for glioma invasion due to the alteration of epithelial-mesenchymal transition and metabolism conversion, particularly influencing mitochondria trafficking and membrane potential (△Ψm). Autopaghy also initiated a feedback on TGF-β2 in glioma by keeping its autocrine loop and affecting Smad2/3/7 expression. A xenograft model provided additional confirmation on combination of TGF-β inhibitor (Galunisertib) and autophagy inhibitor (CQ) to better "turn off" tumor growth.
conclusionOur findings elucidated a potential mechanism of autophagy-associated glioma invasion that TGF-β2 could initiate autophagy via Smad and non-Smad pathway to promote glioma cells' invasion.
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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.