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Loss of LKB1 disrupts breast epithelial cell polarity and promotes breast cancer metastasis and invasion

Overview of attention for article published in Journal of Experimental & Clinical Cancer Research, September 2014
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Title
Loss of LKB1 disrupts breast epithelial cell polarity and promotes breast cancer metastasis and invasion
Published in
Journal of Experimental & Clinical Cancer Research, September 2014
DOI 10.1186/s13046-014-0070-0
Pubmed ID
Authors

Juan Li, Jie Liu, Pingping Li, Xiaona Mao, Wenjie Li, Jin Yang, Peijun Liu

Abstract

BackgroundLKB1, also known as STK11, is a master kinase that serves as an energy metabolic sensor and is involved in cell polarity regulation. Recent studies have indicated that LKB1 is related to breast tumorigenesis and breast cancer progression. However, little work has been done on the roles of LKB1 in cell polarity and epithelial-mesenchymal transition in breast cancer. In this study, we tried to prove that loss of LKB1 disrupts breast epithelial cell polarity and causes tumor metastasis and invasion.MethodsThe relationships of LKB1 expression to clinic-pathological parameters and epithelial markers E-cadherin and high-molecular-weight -cytokeratin (HMW-CK) were investigated in 80 clinical breast cancer tissue samples and their paired normal control breast tissue samples by using immunohistochemistry. Then, the LKB1 expressions in metastatic and non-metastatic breast cancer cell lines were compared. The roles of LKB1 in cell polarity and epithelial-mesenchymal transition in breast cancer were determined by using immunofluorescence, western blot assay, and cell migration and invasive assays. Finally, the non-transformed human breast cell line MCF-10A was cultured in three dimensions to further reveal the role of LKB1 in breast epithelial cell polarity maintenance.ResultsHistopathological analysis showed that LKB1 expression level was significantly negatively correlated with breast cancer TNM stage, and positively correlated with ER/PR status and expression levels of E-cadherin and HMW-CK. Immunofluorescence staining showed that LKB1 was co-localized with E-cadherin at adheren junctions. In vitro analysis revealed that loss of LKB1 expression enhanced migration, invasion and the acquisition of mesenchymal phenotype, while LKB1 overexpression in MDA-MB-435 s cells, which have a low basal level of LKB1 expression, promoted the acquisition of epithelial phenotype. Finally, it was found for the first time that endogenous LKB1 knockdown resulted in abnormal cell polarity in acini formed by non-transformed breast epithelial cells grown in 3D culture.ConclusionOur data indicated that low expression of LKB1 was significantly associated with established markers of unfavorable breast cancer prognosis, such as loss of ER/PR, E-cadherin and HMW-CK. Knockdown of endogenous LKB1 gave rise to dysregulation of cell polarity and invasive phenotype of breast cancer cells.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 61 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Belgium 1 2%
Unknown 60 98%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 17 28%
Student > Bachelor 11 18%
Student > Master 8 13%
Student > Postgraduate 5 8%
Researcher 3 5%
Other 2 3%
Unknown 15 25%
Readers by discipline Count As %
Agricultural and Biological Sciences 18 30%
Medicine and Dentistry 10 16%
Biochemistry, Genetics and Molecular Biology 8 13%
Nursing and Health Professions 2 3%
Pharmacology, Toxicology and Pharmaceutical Science 2 3%
Other 5 8%
Unknown 16 26%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 17 September 2014.
All research outputs
#20,655,488
of 25,373,627 outputs
Outputs from Journal of Experimental & Clinical Cancer Research
#1,635
of 2,378 outputs
Outputs of similar age
#181,729
of 248,614 outputs
Outputs of similar age from Journal of Experimental & Clinical Cancer Research
#12
of 16 outputs
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So far Altmetric has tracked 2,378 research outputs from this source. They receive a mean Attention Score of 4.8. This one is in the 17th percentile – i.e., 17% of its peers scored the same or lower than it.
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