ArticleCell communication and signaling : CCS2026
Translational control of AMPK activity in melanoma.
Article in Cell communication and signaling : CCS, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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
0 citing papers in PubMed.
No citing paper in PubMed yet.
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.
Funding
Abstract
The eIF4F translation initiation complex controls ERK MAPK signaling in malignant melanomas with BRAF and NRAS mutations. It also contributes to the development of melanoma resistance to therapies targeting BRAF and MEK kinases. Here, we uncovered a critical role for eIF4F in regulating the main cellular metabolic sensor, AMP-activated protein kinase (AMPK). In melanoma cells harboring the most common BRAFV600E mutation, ERK and AMPK pathway activities were reported as mutually exclusive. This is because BRAF-driven ERK activity negatively affects LKB1-mediated canonical AMPK activation. However, we observed that eIF4F inhibition can stimulate AMPK activity in melanoma cells, both in vitro and in vivo, despite concomitant ERK hyperactivation. Notably, the protein levels of LKB1 and its co-factor MO25 were sensitive to eIF4F inhibition, indicating a non-canonical LKB1-independent mechanism of AMPK activation. In a proteomic screen, we aimed to identify eIF4F roles in melanoma cell physiology beyond the MAPK pathway. We found that the eIF4F function is essential for maintaining cellular levels of key cell cycle and metabolic regulators, including CDK1, CDK2, TYMS, and UHRF1. Importantly, we also identified the protein phosphatase PP2A as a new eIF4F pathway target. Our subsequent analyses showed that inhibition or siRNA-mediated knockdown of PP2A increases AMPK activity in melanoma cells, independent of LKB1. This data shows that PP2A plays a significant role in regulating AMPK activity in melanoma. Thus, eIF4F inhibition not only impairs canonical AMPK activators but also downregulates PP2A, which negatively regulates AMPK dynamics. Collectively, our data highlight a dual role for eIF4F in controlling AMPK in BRAF-mutant melanoma cells. It maintains the canonical AMPK signaling pathway while simultaneously limiting the extent of AMPK activation via the eIF4F-PP2A-AMPK axis. Pharmacological inhibition of this axis can overcome the negative control of AMPK signaling by the ERK pathway. This suggests new therapeutic opportunities to disrupt melanoma growth.
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.