LKB1 — A master tumour suppressor of the small intestine and beyond

  title={LKB1 — A master tumour suppressor of the small intestine and beyond},
  author={Lina I. Yoo and Daniel C. Chung and Junying Yuan},
  journal={Nature Reviews Cancer},
Peutz–Jeghers syndrome (PJS) is a rare, inherited intestinal polyposis syndrome that is associated with a significantly increased risk of several types of cancer — particularly those of the gastrointestinal and reproductive systems. Most cases of PJS have been associated with loss-of-function mutations in the ubiquitously expressed LKB1 gene, which encodes a serine/ threonine kinase. Recent studies have begun to illustrate the molecular mechanisms by which LKB1 functions as an important new… 

A novel pathogenic splice site variation in STK11 gene results in Peutz–Jeghers syndrome

A novel heterozygous splice-acceptor site variation in the STK11 in a Chinese PJS family is identified, suggesting the mutation may be the causative effect on the dysfunction of the mutant protein.

The molecular mechanisms that underlie the tumor suppressor function of LKB1.

This review focuses on remarkable recent findings concerning the molecular mechanism by which the LKB1 protein kinase operates as a tumor suppressor and discusses the rational treatment strategies to individuals suffering from Peutz-Jeghers syndrome and other common disorders related to L KB1 signaling.

Distinctive gene expression of human lung adenocarcinomas carrying LKB1 mutations

Global expression in lung primary tumors using cDNA microarrays reveals that several important factors contribute to LKB1-mediated carcinogenesis in LADs, confirming previous observations and identifying new putative pathways that should help to elucidate the biological role of L KB1.

Two variants in STK11 gene in Chinese patients with Peutz–Jeghers syndrome

Peutz–Jeghers syndrome (PJS) is an autosomal domi-nant disease manifested as multiple hamartomatous polypsof gastrointestinal tract, mucocutaneous pigmentation andincreased risk of cancers. The

Clinicopathologic and Molecular Features of Pancreatic Adenocarcinoma Associated with Peutz-Jeghers Syndrome

Modeling pancreatic cancer in animal models such as the mouse and zebrafish will further the understanding of the pathogenesis of this important disease, and the studies derived from these model organisms can be potentially applied for developing novel preventive and therapeutic strategies.

Mutations in the human LKB1/STK11 gene

A review of the literature provides a total of 40 different somatic LKB1 mutations in 41 sporadic tumors and seven cancer cell lines, which are concordant with the germline mutation spectrum.

Genetic screening for Peutz–Jeghers syndrome

Based upon the identification of novel mutational mechanisms, the impact of RNA-based screening for germinal STK11/LKB1 mutations in Peutz–Jeghers syndrome are specifically discussed.

Peutz–Jeghers syndrome: genetic screening

Diagnostic and predictive genetic testing is now possible in many families due to identification of causative mutations in the serine/threonine kinase (STK)-11 (also known as the LKB1) gene, which will allow early recognition of the condition in young, at-risk family members.



The Peutz-Jegher gene product LKB1 is a mediator of p53-dependent cell death.

A serine/threonine kinase gene defective in Peutz–Jeghers syndrome

The molecular background of the Peutz–Jeghers syndrome, a rare hereditary disease in which there is predisposition to benign and malignant tumours of many organ systems, is investigated and truncating germline mutations in a gene residing on chromosome 19p are identified.

Mutations in the SMAD4/DPC4 gene in juvenile polyposis.

It is shown that a subset of juvenile polyposis families carry germ line mutations in the gene SMAD4 (also known as DPC4), located on chromosome 18q21.1, that encodes a critical cytoplasmic mediator in the transforming growth factor-beta signaling pathway.

STK11/LKB1 germline mutations are not identified in most Peutz–Jeghers syndrome patients

A novel truncating deletion spanning STK11 exons 2–7 in a single patient and several known polymorphisms are identified, suggesting that STK 11 mutations account for only a proportion of Peutz–Jeghers syndrome cases.

Loss of cytoplasmic retention ability of mutant LKB1 found in Peutz-Jeghers syndrome patients.

It was shown that LKB1 also has a cytoplasmic retention ability which is considered defective and pathogenic in the SL26 mutant, and it is speculated that subcellular distribution of L KB1 is regulated in the balance of these two forces, importation into the nucleus and retention within the cy toplasm.

Allelic imbalance at the LKB1 (STK11) locus in tumours from patients with Peutz‐Jeghers' syndrome provides evidence for a hamartoma–(adenoma)–carcinoma sequence

Molecular evidence that Peutz‐Jeghers' syndrome patients are predisposed to cancers at several sites is provided, as a direct result of selection for loss of the ‘wild‐type’ LKB1 allele in tumours.

Pathogenesis of adenocarcinoma in Peutz-Jeghers syndrome.

Evidence is provided that STK11 is a tumor suppressor gene that acts as an early gatekeeper regulating the development of hamartomas in PJS and suggest that hamartoma may be pathogenetic precursors of adenocarcinoma.

Hamartomatous Polyposis Syndromes: Molecular Genetics, Neoplastic Risk, and Surveillance Recommendations

Genetic alterations underlying hamartomatous polyposis syndromes are diverse and may result from either germ-line mutations in the stroma (JPS) or as a direct result of functional deletion of tumor suppressor genes (PJS).

Peutz-Jeghers families unlinked toSTK11/LKB1 gene mutations are highly predisposed to primitive biliary adenocarcinoma

Up to 30% of Peutz-Jeghers syndrome patients are caused by mutation in an unidentified gene that confers high susceptibility to cancer development, and patients with no identified STK11/LKB1 mutation are at major risk for proximal biliary adenocarcinoma, an infrequent tumour in the general population.

Gastrointestinal hamartomatous polyposis in Lkb1 heterozygous knockout mice.

The data strongly suggest that the initiation of polyposis is not the result of loss of heterozygosity in Lkb1, and that the gastrointestinal hamartomas appear to develop because of the LKB1 haploinsufficiency.