ArticleGastroenterology2010
LKB1 haploinsufficiency cooperates with Kras to promote pancreatic cancer through suppression of p21-dependent growth arrest.
Article in Gastroenterology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 96 papers, 5 of them syntheses that pooled it.
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
96 citing papers in PubMed, 5 syntheses or guidelines pooled it, 159 citations in OpenAlex.
- Clinicopathological and prognostic significance of LKB1 expression in gastric cancer: a systematic review and meta-analysis.Scientific reports · 2023Pooled it
- Pooled it
- Association between LKB1 expression and prognosis of patients with solid tumours: an updated systematic review and meta-analysis.BMJ open · 2019Pooled it
- Construction of a prognostic prediction system for pancreatic ductal adenocarcinoma to investigate the key prognostic genes.Molecular medicine reports · 2018Pooled it
- Pooled it
- Integrating germline and tumor sequencing to improve hereditary cancer diagnosis and care.European journal of human genetics : EJHG · 2026Review
- Liver Kinase B1 in CD11cAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Proteomic Perspectives on KRAS-Driven Cancers and Emerging Therapeutic Approaches.Current oncology (Toronto, Ont.) · 2025Review
- Loss of Lkb1 cooperates with BrafMolecular oncology · 2025Article
- The role of LKB1 in prostate cancer: implications for tumor progression and therapy.Frontiers in cell and developmental biology · 2025Review
- Discovery of the Natural Bibenzyl Compound Erianin in Dendrobium Inhibiting the Growth and EMT of Gastric Cancer through Downregulating the LKB1-SIK2/3-PARD3 Pathway.International journal of molecular sciences · 2024Article
- Cytokine CCL9 Mediates Oncogenic KRAS-Induced Pancreatic Acinar-to-Ductal Metaplasia by Promoting Reactive Oxygen Species and Metalloproteinases.International journal of molecular sciences · 2024Article
- The role of STK11/LKB1 in cancer biology: implications for ovarian tumorigenesis and progression.Frontiers in cell and developmental biology · 2024Review
- Senescence program and its reprogramming in pancreatic premalignancy.Cell death & disease · 2023Review
- LKB1 controls inflammatory potential through CRTC2-dependent histone acetylation.Molecular cell · 2023Article
- RBM4 dictates ESCC cell fate switch from cellular senescence to glutamine-addiction survival through inhibiting LKB1-AMPK-axis.Signal transduction and targeted therapy · 2023Article
- Clinical and Molecular Attributes and Evaluation of Pancreatic Cystic Neoplasm.Biochimica et biophysica acta. Reviews on cancer · 2023Review
- FN1 encoding fibronectin as a pivotal signaling gene for therapeutic intervention against pancreatic cancer.Molecular genetics and genomics : MGG · 2022Article
- Mouse models of Kras activation in gastric cancer.Experimental & molecular medicine · 2022Review
- LKB1 is physiologically required for sleep from Drosophila melanogaster to the Mus musculus.Genetics · 2022Article
36 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issuedCorrigendum.2024
Authors and funding
14 authors at 5 institutions in 1 country.
Funding
Abstract
BACKGROUND &
aimsPatients carrying germline mutations of LKB1 have an increased risk of pancreatic cancer; however, it is unclear whether down-regulation of LKB1 is an important event in sporadic pancreatic cancer. In this study, we aimed to investigate the impact of LKB1 down-regulation for pancreatic cancer in mouse and human and to elucidate the mechanism by which Lkb1 deregulation contributes to this disease.
methodsWe first investigated the consequences of Lkb1 deficiency in a genetically modified mouse model of pancreatic cancer, both in terms of disease progression and at the molecular level. To test the relevance of our findings to human pancreatic cancer, we investigated levels of LKB1 and its potential targets in human pancreatic cancer.
resultsWe definitively show that Lkb1 haploinsufficiency can cooperate with oncogenic KrasG12D to cause pancreatic ductal adenocarcinoma (PDAC) in the mouse. Mechanistically, this was associated with decreased p53/p21-dependent growth arrest. Haploinsufficiency for p21 (Cdkn1a) also synergizes with KrasG12D to drive PDAC in the mouse. We also found that levels of LKB1 expression were decreased in around 20% of human PDAC and significantly correlated with low levels of p21 and a poor prognosis. Remarkably, all tumors that had low levels of LKB1 had low levels of p21, and these tumors did not express mutant p53.
conclusionsWe have identified a novel LKB1-p21 axis that suppresses PDAC following Kras mutation in vivo. Down-regulation of LKB1 may therefore serve as an alternative to p53 mutation to drive pancreatic cancer in vivo.
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.