ArticleResearch square2026
Glutamine stress promotes metastatic potential via hexosamine biosynthetic pathway activity in KRAS/STK11-mutant lung adenocarcinoma.
Article in Research square, 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
9 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Lung cancer is the leading cause of cancer-related deaths worldwide. Loss of STK11 in KRAS-driven lung adenocarcinoma (LUAD) is observed in approximately 15,000 US lung cancer cases annually and drives an aggressive, resistant disease. STK11 regulates many cellular processes, including metabolism, and loss of this tumor suppressor drives a "glutamine addicted" phenotype that is being considered for targeted therapy. However, recent work from our group revealed the activation of pro-oncogenic signaling in KRAS/STK11-mutant LUAD cells upon glutamine deprivation, suggesting the development of an advantageous adaptation. Here, we demonstrate that STK11 loss in KRAS-driven LUAD cells increases glutamine-dependent mitochondrial respiration, which is metabolically rewired upon exogenous glutamine deprivation to enhance the hexosamine biosynthetic pathway (HBP). Furthermore, our results reveal that enhanced HBP flux in STK11 null KRAS-driven LUAD cells promotes a pro-metastatic phenotype characterized by adherent cell detachment, resistance to apoptosis, and 3D spheroid invasion. This study highlights, for the first time, enhanced HBP flux as a protective shunt in response to glutamine deprivation in KRAS/STK11-mutant LUAD. Our results challenge the potential benefit of glutamine deprivation as a therapeutic intervention in this patient population. Future work aims to further elucidate the role of the HBP in promoting metastasis and to determine the mechanism(s) by which STK11 null KRAS-driven LUAD cells upregulate the HBP.
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.