ArticleOncotarget2014
Noxa upregulation by oncogenic activation of MEK/ERK through CREB promotes autophagy in human melanoma cells.
Article in Oncotarget, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis that pooled it.
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Who cites it
25 citing papers in PubMed, 1 synthesis or guideline pooled it, 41 citations in OpenAlex.
- Tumor growth suppression by inhibiting both autophagy and STAT3 signaling in HNSCC.Oncotarget · 2015Pooled it
- ERK1/2 Signaling in Intrahepatic Cholangiocarcinoma: From Preclinical Advances to Therapeutic Strategies.Biology · 2025Review
- Interplay between MAPK signaling pathway and autophagy in skin aging: mechanistic insights and therapeutic implications.Frontiers in cell and developmental biology · 2025Review
- Targeting CREBRF in Cancer: Mechanistic Insights and Future Directions.Biologics : targets & therapy · 2025Review
- The interplay of mitophagy, autophagy, and apoptosis in cisplatin-induced kidney injury: involvement of ERK signaling pathway.Cell death discovery · 2024Article
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- Targeting MCL-1 protein to treat cancer: opportunities and challenges.Frontiers in oncology · 2023Review
- IKKε knockout alleviates angiotensin II-induced apoptosis and excessive autophagy in vascular smooth muscle cells by regulating the ERK1/2 pathway.Experimental and therapeutic medicine · 2021Article
- Suppressing ERK Pathway Impairs Glycochenodeoxycholate-Mediated Survival and Drug-Resistance in Hepatocellular Carcinoma Cells.Frontiers in oncology · 2021Article
- Non-Apoptotic Cell Death Signaling Pathways in Melanoma.International journal of molecular sciences · 2020Review
- Overcoming Resistance to Therapies Targeting the MAPK Pathway in BRAF-Mutated Tumours.Journal of oncology · 2020Review
- CB002, a novel p53 tumor suppressor pathway-restoring small molecule induces tumor cell death through the pro-apoptotic protein NOXA.Cell cycle (Georgetown, Tex.) · 2018Article
- Mechanisms and prevention of UV-induced melanoma.Photodermatology, photoimmunology & photomedicine · 2018Review
- Metabolic strategies of melanoma cells: Mechanisms, interactions with the tumor microenvironment, and therapeutic implications.Pigment cell & melanoma research · 2018Review
- EPAC-RAP1 Axis-Mediated Switch in the Response of Primary and Metastatic Melanoma to Cyclic AMP.Molecular cancer research : MCR · 2017Article
- Control of cell death and mitochondrial fission by ERK1/2 MAP kinase signalling.The FEBS journal · 2017Review
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- MicroRNA-645 is an oncogenic regulator in colon cancer.Oncogenesis · 2017Article
- The tubulin inhibitor MG-2477 induces autophagy-regulated cell death, ROS accumulation and activation of FOXO3 in neuroblastoma.Oncotarget · 2017Article
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Reduction in the expression of the anti-survival BH3-only proteins PUMA and Bim is associated with the pathogenesis of melanoma. However, we have found that the expression of the other BH3-only protein Noxa is commonly upregulated in melanoma cells, and that this is driven by oncogenic activation of MEK/ERK. Immunohistochemistry studies showed that Noxa was expressed at higher levels in melanomas than nevi. Moreover, the expression of Noxa was increased in metastatic compared to primary melanomas, and in thick primaries compared to thin primaries. Inhibition of oncogenic BRAFV600E or MEK downregulated Noxa, whereas activation of MEK/ERK caused its upregulation. In addition, introduction of BRAFV600E increased Noxa expression in melanocytes. Upregulation of Noxa was due to a transcriptional increase mediated by cAMP responsive element binding protein, activation of which was also increased by MEK/ERK signaling in melanoma cells. Significantly, Noxa appeared necessary for constitutive activation of autophagy, albeit at low levels, by MEK/ERK in melanoma cells. Furthermore, it was required for autophagy activation that delayed apoptosis in melanoma cells undergoing nutrient deprivation. These results reveal that oncogenic activation of MEK/ERK drives Noxa expression to promote autophagy, and suggest that Noxa has an indirect anti-apoptosis role in melanoma cells under nutrient starvation conditions.
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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.