Liver Kinase B1 Signaling in Cancer Metabolism

Liver Kinase B1 (LKB1) is a master regulatory kinase that orchestrates cellular energy homeostasis by activating downstream effectors such as AMP-activated protein kinase (AMPK). Through this axis, LKB1 balances anabolic and catabolic processes in response to nutrient and energetic stress. In cancer, loss or mutation of LKB1 rewires metabolic programmes, enhancing glycolysis, lipid synthesis and glutamine dependency while disabling stress-response checkpoints. This metabolic rewiring supports rapid proliferation but also uncovers vulnerabilities that can be therapeutically exploited. Beyond bioenergetics, LKB1 influences cell polarity, epigenetic states and inflammatory gene expression, integrating metabolic cues with transcriptional control. Deficiencies in LKB1 signalling are observed in a spectrum of malignancies—including non-small-cell lung cancer, pancreatic ductal adenocarcinoma and cervical carcinoma—where they correlate with aggressive behaviour and poor prognosis. Understanding how LKB1 loss shapes tumour metabolism has yielded novel strategies to stress cancer cells selectively through nutrient deprivation, targeted metabolic inhibitors and combination regimens that restore energetic control.

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Liver Kinase B1 Signaling in Cancer Metabolism publication trend

The graph below shows the total number of articles in liver kinase b1 signaling in cancer metabolism across all publications each year (not limited to Nature Index journals).

Technical terms

Liver Kinase B1 (LKB1): A serine/threonine kinase that senses energy status and activates pathways to restore balance.

AMP-activated protein kinase (AMPK): A central energy sensor that inhibits growth pathways and stimulates catabolism when cellular energy is low.

Mechanistic target of rapamycin (mTOR): A kinase that promotes cell growth and protein synthesis in response to nutrients and growth factors.

Glutaminolysis: Metabolic process by which glutamine is converted into intermediates that fuel the tricarboxylic acid cycle and biosynthesis.

Ubiquitination: The attachment of ubiquitin molecules to a protein, often marking it for proteasomal degradation.

Histone acetylation: The addition of acetyl groups to histone tails, loosening chromatin structure and promoting gene transcription.

References

1. RBM4 dictates ESCC cell fate switch from cellular senescence to glutamine-addiction survival through inhibiting LKB1-AMPK-axis. Signal Transduction and Targeted Therapy (2023).
2. LKB1-dependent regulation of TPI1 creates a divergent metabolic liability between human and mouse lung adenocarcinoma. Cancer Discovery (2023).
3. LKB1 controls inflammatory potential through CRTC2-dependent histone acetylation. Molecular Cell (2023).
4. Caloric restriction and metformin selectively improved LKB1-mutated NSCLC tumor response to chemo- and chemo-immunotherapy. Journal of Experimental & Clinical Cancer Research (2024).
5. Somatic LKB1 Mutations Promote Cervical Cancer Progression. PLOS ONE (2009).
6. Loss of LKB1 disrupts breast epithelial cell polarity and promotes breast cancer metastasis and invasion. Journal of Experimental & Clinical Cancer Research (2014).
7. LKB1 Haploinsufficiency Cooperates With Kras to Promote Pancreatic Cancer Through Suppression of p21-Dependent Growth Arrest. Gastroenterology (2010).