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Inhibition of Six1 affects tumour invasion and the expression of cancer stem cell markers in pancreatic cancer

Overview of attention for article published in BMC Cancer, April 2017
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Title
Inhibition of Six1 affects tumour invasion and the expression of cancer stem cell markers in pancreatic cancer
Published in
BMC Cancer, April 2017
DOI 10.1186/s12885-017-3225-5
Pubmed ID
Authors

Tristan Lerbs, Savita Bisht, Sebastian Schölch, Mathieu Pecqueux, Glen Kristiansen, Martin Schneider, Bianca T. Hofmann, Thilo Welsch, Christoph Reissfelder, Nuh N. Rahbari, Johannes Fritzmann, Peter Brossart, Jürgen Weitz, Georg Feldmann, Christoph Kahlert

Abstract

Epithelial-to-mesenchymal transition (EMT) and cancer stem cells (CSC) contribute to tumour progression and metastasis. Assessment of transcription factors involved in these two mechanisms can help to identify new targets for an oncological therapy. In this study, we focused on the evaluation of the transcription factor Six1 (Sine oculis 1). This protein is involved in embryologic development and its contribution to carcinogenesis has been described in several studies. Immunohistochemistry against Six1 was performed on a tissue microarray containing specimens of primary pancreatic ductal adenocarcinomas (PDAC) of 139 patients. Nuclear and cytoplasmic expression was evaluated and correlated to histopathological parameters. Expression of Six1 was inhibited transiently by siRNA in Panc1 and BxPc3 cells and stably by shRNA in Panc1 cells. Expression analysis of CDH1 and Vimentin mRNA was performed and cell motility was tested in a migration assay. Panc1 cells transfected with Six1 shRNA or scrambled shRNA were injected subcutaneously into nude mice. Tumour growth was observed for four weeks. Afterwards, tumours were stained against Six1, CD24 and CD44. Six1 was overexpressed in the cytoplasm and cellular nuclei in malignant tissues (p < 0.0001). No correlation to histopathological parameters could be detected. Six1 down-regulation decreased pancreatic cancer cell motility in vitro. CDH1 and vimentin expression was decreased after inhibition of the expression of Six1. Pancreatic tumours with impaired expression of Six1 showed significantly delayed growth and displayed loss of the CD24(+)/CD44(+) phenotype. We show that Six1 is overexpressed in human PDAC and that its inhibition results in a decreased tumour progression in vitro and in vivo. Therefore, targeting Six1 might be a novel therapeutic approach in patients with pancreatic cancer.

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The data shown below were collected from the profile of 1 X user who shared this research output. Click here to find out more about how the information was compiled.
Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 29 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 29 100%

Demographic breakdown

Readers by professional status Count As %
Student > Bachelor 5 17%
Researcher 5 17%
Student > Ph. D. Student 4 14%
Professor > Associate Professor 2 7%
Student > Master 2 7%
Other 1 3%
Unknown 10 34%
Readers by discipline Count As %
Medicine and Dentistry 8 28%
Biochemistry, Genetics and Molecular Biology 6 21%
Agricultural and Biological Sciences 3 10%
Pharmacology, Toxicology and Pharmaceutical Science 1 3%
Chemistry 1 3%
Other 0 0%
Unknown 10 34%
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 14 April 2017.
All research outputs
#20,413,129
of 22,963,381 outputs
Outputs from BMC Cancer
#6,522
of 8,345 outputs
Outputs of similar age
#270,111
of 309,935 outputs
Outputs of similar age from BMC Cancer
#103
of 135 outputs
Altmetric has tracked 22,963,381 research outputs across all sources so far. This one is in the 1st percentile – i.e., 1% of other outputs scored the same or lower than it.
So far Altmetric has tracked 8,345 research outputs from this source. They receive a mean Attention Score of 4.3. This one is in the 1st percentile – i.e., 1% of its peers scored the same or lower than it.
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We're also able to compare this research output to 135 others from the same source and published within six weeks on either side of this one. This one is in the 1st percentile – i.e., 1% of its contemporaries scored the same or lower than it.