ArticleThe Journal of biological chemistry2014
67-kDa laminin receptor-dependent protein phosphatase 2A (PP2A) activation elicits melanoma-specific antitumor activity overcoming drug resistance.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
30 citing papers in PubMed, 70 citations in OpenAlex.
- Green Tea Polyphenol (-)-Epigallocatechin-3-gallate Protects Endothelial Barrier Function via Myosin Phosphatase and Rho-Kinase.International journal of molecular sciences · 2026Article
- Low Brain Levels of Dietary Polyphenols and Their Conjugates: Reassessing Mechanisms of Alzheimer's Disease Prevention.Journal of dementia and alzheimer's disease · 2026Article
- Delphinidin upregulates microRNA-let-7b expression through family with sequence similarity 222 member B.Scientific reports · 2025Article
- Epigallocatechin Gallate (EGCG): Pharmacological Properties, Biological Activities and Therapeutic Potential.Molecules (Basel, Switzerland) · 2025Review
- The anti-cancer effect of epigallocatechin-3-O-gallate against multiple myeloma cells is potentiated by 5,7-dimethoxyflavone.FEBS open bio · 2023Article
- Epigallocatechin-3-Gallate Therapeutic Potential in Cancer: Mechanism of Action and Clinical Implications.Molecules (Basel, Switzerland) · 2023Review
- Epigallocatechin gallate restores the reduction of protein phosphatase 2 A subunit B caused by middle cerebral artery occlusion.Laboratory animal research · 2023Article
- Vitamin E functions by association with a novel binding site on the 67 kDa laminin receptor activating diacylglycerol kinase.The Journal of nutritional biochemistry · 2022Article
- The Role of Diacylglycerol Kinase in the Amelioration of Diabetic Nephropathy.Molecules (Basel, Switzerland) · 2022Review
- 67-kDa Laminin Receptor-Mediated Cellular Sensing System of Green Tea Polyphenol EGCG and Functional Food Pairing.Molecules (Basel, Switzerland) · 2022Review
- Ethanol Metabolism in the Liver, the Induction of Oxidant Stress, and the Antioxidant Defense System.Antioxidants (Basel, Switzerland) · 2022Review
- Article
- Anticarcinogenic potentials of tea catechins.Frontiers in nutrition · 2022Review
- Natural biomolecules and derivatives as anticancer immunomodulatory agents.Frontiers in immunology · 2022Review
- The Effect of Green Tea as an Adjuvant to Enzyme Replacement Therapy on Oxidative Stress in Fabry Disease: A Pilot Study.Frontiers in nutrition · 2022Article
- LAMR1 restricts Zika virus infection by attenuating the envelope protein ubiquitination.Virulence · 2021Article
- Myosin Phosphatase Is Implicated in the Control of THP-1 Monocyte to Macrophage Differentiation.International journal of molecular sciences · 2021Article
- Src Mediates Epigallocatechin-3-Molecules (Basel, Switzerland) · 2020Article
- Review
- The mechanisms of ameliorating effect of a green tea polyphenol on diabetic nephropathy based on diacylglycerol kinase α.Scientific reports · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The Ras/Raf/MEK/ERK pathway has been identified as a major, druggable regulator of melanoma. Mutational activation of BRAF is the most prevalent genetic alteration in human melanoma, resulting in constitutive melanoma hyperproliferation. A selective BRAF inhibitor showed remarkable clinical activity in patients with mutated BRAF. Unfortunately, most patients acquire resistance to the BRAF inhibitor, highlighting the urgent need for new melanoma treatment strategies. Green tea polyphenol (-)-epigallocatechin-3-O-gallate (EGCG) inhibits cell proliferation independently of BRAF inhibitor sensitivity, suggesting that increased understanding of the anti-melanoma activity of EGCG may provide a novel therapeutic target. Here, by performing functional genetic screening, we identified protein phosphatase 2A (PP2A) as a critical factor in the suppression of melanoma cell proliferation. We demonstrated that tumor-overexpressed 67-kDa laminin receptor (67LR) activates PP2A through adenylate cyclase/cAMP pathway eliciting inhibitions of oncoproteins and activation of tumor suppressor Merlin. Activating 67LR/PP2A pathway leading to melanoma-specific mTOR inhibition shows strong synergy with the BRAF inhibitor PLX4720 in the drug-resistant melanoma. Moreover, SET, a potent inhibitor of PP2A, is overexpressed on malignant melanoma. Silencing of SET enhances 67LR/PP2A signaling. Collectively, activation of 67LR/PP2A signaling may thus be a novel rational strategy for melanoma-specific treatment.
Indexed as
Identifiers
What OpenQuestion holds
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.