ArticleCancer science2015
Transforming growth factor-β signaling enhancement by long-term exposure to hypoxia in a tumor microenvironment composed of Lewis lung carcinoma cells.
Article in Cancer science, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 35 citations in OpenAlex.
- Hippo signaling pathway regulates branching morphogenesis of the fetal lung under hypoxia.Pediatric research · 2026Article
- Pmel17 Deficiency Affects Melanogenesis and Promotes Tumor Vascularization.International journal of molecular sciences · 2026Article
- PDGFRα governs multiple cellular signals and plays a protective role in tumor progression.Neoplasia (New York, N.Y.) · 2026Article
- Interplay of HIF-1α, SMAD2, and VEGF signaling in hypoxic renal environments: impact on macrophage polarization and renoprotection.Renal failure · 2025Article
- Non-small cell lung cancer map and analysis: exploring interconnected oncogenic signal integrators.Mammalian genome : official journal of the International Mammalian Genome Society · 2025Article
- USP9X integrates TGF-β and hypoxia signalings to promote ovarian cancer chemoresistance via HIF-2α-maintained stemness.Cell death & disease · 2025Article
- Article
- The role of oxygen tension in cell fate and regenerative medicine: implications of hypoxia/hyperoxia and free radicals.Cell and tissue banking · 2024Review
- Involvement of Epithelial-Mesenchymal Transition (EMT) in Autoimmune Diseases.International journal of molecular sciences · 2023Review
- Immunotherapy for lung cancer combining the oligodeoxynucleotides of TLR9 agonist and TGF-β2 inhibitor.Cancer immunology, immunotherapy : CII · 2023Article
- Increase in transforming growth factor-β didnot affect trombospondin1 in preeclampsia placentas.Turkish journal of obstetrics and gynecology · 2023Article
- Implantation and tracing of green fluorescent protein-expressing adipose-derived stem cells in peri-implant capsular fibrosis.Stem cell research & therapy · 2023Article
- Cell-Type Dependent Regulation of the Electrogenic NaInternational journal of molecular sciences · 2022Article
- Review
- Review
- Identification of Key microRNAs and Genes in Infantile Hemangiomas.Frontiers in genetics · 2022Article
- Endothelial-specific depletion of TGF-β signaling affects lymphatic function.Inflammation and regeneration · 2021Article
- Ginsenoside CK Inhibits Hypoxia-Induced Epithelial-Mesenchymal Transformation through the HIF-1α/NF-κB Feedback Pathway in Hepatocellular Carcinoma.Foods (Basel, Switzerland) · 2021Article
- Hypoxia-induced epithelial to mesenchymal transition in cancer.Cancer letters · 2020Review
- The evolutionarily conserved deubiquitinase UBH1/UCH-L1 augments DAF7/TGF-β signaling, inhibits dauer larva formation, and enhances lung tumorigenesis.The Journal of biological chemistry · 2020Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Transforming growth factor-β (TGF-β) is a potent growth inhibitor in normal epithelial cells. However, a number of malignant tumors produce excessive amounts of TGF-β, which affects the tumor-associated microenvironment by furthering the progression of tumorigenicity. Although it is known that the tumor-associated microenvironment often becomes hypoxic, how hypoxia influences TGF-β signaling in this microenvironment is unknown. We investigated whether TGF-β signaling is influenced by long-term exposure to hypoxia in Lewis lung carcinoma (LLC) cells. When the cells were exposed to hypoxia for more than 10 days, their morphology was remarkably changed to a spindle shape, and TGF-β-induced Smad2 phosphorylation was enhanced. Concomitantly, TGF-β-induced transcriptional activity was augmented under hypoxia, although TGF-β did not influence the activity of a hypoxia-responsive reporter. Consistently, hypoxia influenced the expression of several TGF-β target genes. Interestingly, the expressions of TGF-β type I receptor (TβRI), also termed activin receptor like kinase-5 (ALK5), and TGF-β1 were increased under the hypoxic condition. When we monitored the hypoxia-inducible factor-1 (HIF-1) transcriptional activity by use of green fluorescent protein governed by the hypoxia-responsive element in LLC cells transplanted into mice, TGF-β-induced Smad2 phosphorylation was upregulated in vivo. Our results demonstrate that long-term exposure to hypoxia might alter responsiveness to TGF-β signaling and affected the malignancy of LLC cells.
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