ArticleScience advances2021
MAPK6-AKT signaling promotes tumor growth and resistance to mTOR kinase blockade.
Article in Science advances, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
What it found
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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.
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Who cites it
20 citing papers in PubMed, 31 citations in OpenAlex.
- LINC01996 suppresses non-small cell lung cancer proliferation and metastasis by orchestrating the miR-12115/CNRIP1/Ras signaling axis.Clinical & experimental metastasis · 2026Article
- Intracellular pH regulates ubiquitin-mediated degradation of the MAP kinase ERK3.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- NPR1 Promotes Lipid Droplet Lipolysis to Enhance Mitochondrial Oxidative Phosphorylation and Fuel Gastric Cancer Metastasis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Pathology-inspired collagen-binding thermosensitive micelle drops enable prolonged and efficient treatment of fungal keratitis.Bioactive materials · 2025Article
- Identification of characteristic genes ofanddeficiency constitutions: an integrated analysis based on bioinformatics and machine learning.Journal of traditional Chinese medicine = Chung i tsa chih ying wen pan · 2025Article
- Association of Lutein with Cancer: A Systematic Review of the Lutein Effects on Cellular Processes Involved in Cancer Progression.Preventive nutrition and food science · 2025Article
- SERPINA1 methylation as a novel diagnostic marker for early-stage papillary thyroid carcinoma via MAPK6-AKT/mTOR pathway.Clinical epigenetics · 2025Article
- Differential gene expression analysis in French bulldog high grade oligodendroglioma: breed-associated differences in tumor and tumor microenvironment gene expression.Companion animal health and genetics · 2025Article
- Atypical MAPKs in cancer.The FEBS journal · 2025Review
- Disturbed shear stress promotes atherosclerosis through TRIM21-regulated MAPK6 degradation and consequent endothelial inflammation.Clinical and translational medicine · 2025Article
- ERK3/MAPK6 promotes triple-negative breast cancer progression through collective migration and EMT plasticity.Frontiers in oncology · 2025Article
- Review
- The mTORC2 signaling network: targets and cross-talks.The Biochemical journal · 2024Review
- NUAK1 coordinates growth factor-dependent activation of mTORC2 and Akt signaling.Cell & bioscience · 2023Article
- MALAT1 expression is associated with aggressive behavior in indolent B-cell neoplasms.Scientific reports · 2023Article
- Cooperative activation of PDK1 and AKT by MAPK4 enhances cancer growth and resistance to therapy.PLoS biology · 2023Article
- Increased methylation of ZNF671 suppresses tumor progression by promoting MAPK6 transcription in laryngeal carcinoma.International journal of biological sciences · 2023Article
- ERK3 and DGKζ interact to modulate cell motility in lung cancer cells.Frontiers in cell and developmental biology · 2023Article
- Article
- A COP1-GATA2 axis suppresses AR signaling and prostate cancer.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
Mitogen-activated protein kinase 6 (MAPK6) is an atypical MAPK. Its function in regulating cancer growth remains elusive. Here, we reported that MAPK6 directly activated AKT and induced oncogenic outcomes. MAPK6 interacted with AKT through its C34 region and the C-terminal tail and phosphorylated AKT at S473 independent of mTORC2, the major S473 kinase. mTOR kinase inhibitors have not made notable progress in the clinic. Our identified MAPK6-AKT axis may provide a major resistance pathway. Besides repressing growth, inhibiting MAPK6 sensitized cancer cells to mTOR kinase inhibitors. MAPK6 overexpression is associated with decreased overall survival and the survival of patients with lung adenocarcinoma, mesothelioma, uveal melanoma, and breast cancer. MAPK6 expression also correlated with AKT phosphorylation at S473 in human cancer tissues. We conclude that MAPK6 can promote cancer by activating AKT independent of mTORC2 and targeting MAPK6, either alone or in combination with mTOR blockade, may be effective in cancers.
Identifiers
What Socratic 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 Socratic graph.