ArticleCarcinogenesis2018
Deficiency of tumor suppressor Merlin facilitates metabolic adaptation by co-operative engagement of SMAD-Hippo signaling in breast cancer.
Article in Carcinogenesis, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 37 citations in OpenAlex.
- Noncoding RNAs in Metabolic Reprogramming of Breast Cancer: Dietary Opportunities and Translational Implications.Experientia supplementum (2012) · 2026Review
- Roles of TEAD Transcription Factors and their Coactivators in the Progression and Metastasis of Cancers.Recent patents on anti-cancer drug discovery · 2026Review
- Gracillin suppresses cancer progression through inducing Merlin/LATS protein-protein interaction and activating Hippo signaling pathway.Acta pharmacologica Sinica · 2025Article
- Interactions among Merlin, Arkadia, and SKOR2 mediate NF2-associated human Schwann cell proliferation.Stem cell research & therapy · 2025Article
- Bcl-2 dependent modulation of Hippo pathway in cancer cells.Cell communication and signaling : CCS · 2024Article
- The Role of Urothelial Cancer-Associated 1 in Gynecological Cancers.Current issues in molecular biology · 2024Review
- Roles of TGF‑β signalling pathway‑related lncRNAs in cancer (Review).Oncology letters · 2023Review
- Prognostic and diagnostic values of non-coding RNAs as biomarkers for breast cancer: An umbrella review and pan-cancer analysis.Frontiers in molecular biosciences · 2023Article
- Long non-coding RNAs affecting cell metabolism in cancer.Biology direct · 2022Review
- Review
- lncRNAs: Key Regulators of Signaling Pathways in Tumor Glycolysis.Disease markers · 2022Review
- Inhibin βA is an independent prognostic factor that promotes invasion via Hippo signaling in non‑small cell lung cancer.Molecular medicine reports · 2021Article
- Metabolic landscapes in sarcomas.Journal of hematology & oncology · 2021Review
- Utilizing the Hippo pathway as a therapeutic target for combating endocrine-resistant breast cancer.Cancer cell international · 2021Review
- Integrated Metabolomics and Transcriptomics Using an Optimised Dual Extraction Process to Study Human Brain Cancer Cells and Tissues.Metabolites · 2021Article
- Merlin deficiency alters the redox management program in breast cancer.Molecular oncology · 2021Article
- Regulatory Mechanisms of LncRNAs in Cancer Glycolysis: Facts and Perspectives.Cancer management and research · 2021Review
- Cytoskeletal Remodeling in Cancer.Biology · 2020Review
- CircTBL1XR1/miR-424 axis regulates Smad7 to promote the proliferation and metastasis of colorectal cancer.Journal of gastrointestinal oncology · 2020Article
- The crosstalk between lncRNAs and the Hippo signalling pathway in cancer progression.Cell proliferation · 2020Review
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
The NF2 gene encodes the tumor and metastasis suppressor protein Merlin. Merlin exerts its tumor suppressive role by inhibiting proliferation and inducing contact-growth inhibition and apoptosis. In the current investigation, we determined that loss of Merlin in breast cancer tissues is concordant with the loss of the inhibitory SMAD, SMAD7, of the TGF-β pathway. This was reflected as dysregulated activation of TGF-β signaling that co-operatively engaged with effectors of the Hippo pathway (YAP/TAZ/TEAD). As a consequence, the loss of Merlin in breast cancer resulted in a significant metabolic and bioenergetic adaptation of cells characterized by increased aerobic glycolysis and decreased oxygen consumption. Mechanistically, we determined that the co-operative activity of the Hippo and TGF-β transcription effectors caused upregulation of the long non-coding RNA Urothelial Cancer-Associated 1 (UCA1) that disengaged Merlin's check on STAT3 activity. The consequent upregulation of Hexokinase 2 (HK2) enabled a metabolic shift towards aerobic glycolysis. In fact, Merlin deficiency engendered cellular dependence on this metabolic adaptation, endorsing a critical role for Merlin in regulating cellular metabolism. This is the first report of Merlin functioning as a molecular restraint on cellular metabolism. Thus, breast cancer patients whose tumors demonstrate concordant loss of Merlin and SMAD7 may benefit from an approach of incorporating STAT3 inhibitors.
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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.