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MEK Inhibition Targets Cancer Stem Cells and Impedes Migration of Pancreatic Cancer Cells In Vitro and In Vivo
Joint Authors
Seufferlein, Thomas
Sainz, Bruno
Hermann, Patrick C.
Gout, Johann
Walter, Karolin
Tiwary, Kanishka
Trajkovic-Arsic, Marija
Hidalgo-Sastre, Ana
Dierichs, Laura
Liffers, Sven T.
Gu, Jiangning
Schulte, Lucas-Alexander
Münch, Jan
Siveke, Jens T.
Rodriguez-Aznar, Eva
Source
Issue
Vol. 2019, Issue 2019 (31 Dec. 2019), pp.1-11, 11 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2019-06-02
Country of Publication
Egypt
No. of Pages
11
Abstract EN
Pancreatic ductal adenocarcinoma (PDAC) remains a devastating disease with a very poor prognosis.
At the same time, its incidence is on the rise, and PDAC is expected to become the second leading cause of cancer-related death by 2030.
Despite extensive work on new therapeutic approaches, the median overall survival is only 6-12 months after diagnosis and the 5-year survival is less than 7%.
While pancreatic cancer is particularly difficult to treat, patients usually succumb not to the growth of the primary tumor, but to extensive metastasis; therefore, strategies to reduce the migratory and metastatic capacity of pancreatic cancer cells merit close attention.
The vast majority of pancreatic cancers harbor RAS mutations.
The outstanding relevance of the RAS/MEK/ERK pathway in pancreatic cancer biology has been extensively shown previously.
Due to their high dependency on Ras mutations, pancreatic cancers might be particularly sensitive to inhibitors acting downstream of Ras.
Herein, we use a genetically engineered mouse model of pancreatic cancer and primary pancreatic cancer cells were derived from this model to demonstrate that small-molecule MEK inhibitors functionally abrogate cancer stem cell populations as demonstrated by reduced sphere and organoid formation capacity.
Furthermore, we demonstrate that MEK inhibition suppresses TGFβ-induced epithelial-to-mesenchymal transition and migration in vitro and ultimately results in a highly significant reduction in circulating tumor cells in mice.
American Psychological Association (APA)
Walter, Karolin& Tiwary, Kanishka& Trajkovic-Arsic, Marija& Hidalgo-Sastre, Ana& Dierichs, Laura& Liffers, Sven T.…[et al.]. 2019. MEK Inhibition Targets Cancer Stem Cells and Impedes Migration of Pancreatic Cancer Cells In Vitro and In Vivo. Stem Cells International،Vol. 2019, no. 2019, pp.1-11.
https://search.emarefa.net/detail/BIM-1209761
Modern Language Association (MLA)
Walter, Karolin…[et al.]. MEK Inhibition Targets Cancer Stem Cells and Impedes Migration of Pancreatic Cancer Cells In Vitro and In Vivo. Stem Cells International No. 2019 (2019), pp.1-11.
https://search.emarefa.net/detail/BIM-1209761
American Medical Association (AMA)
Walter, Karolin& Tiwary, Kanishka& Trajkovic-Arsic, Marija& Hidalgo-Sastre, Ana& Dierichs, Laura& Liffers, Sven T.…[et al.]. MEK Inhibition Targets Cancer Stem Cells and Impedes Migration of Pancreatic Cancer Cells In Vitro and In Vivo. Stem Cells International. 2019. Vol. 2019, no. 2019, pp.1-11.
https://search.emarefa.net/detail/BIM-1209761
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1209761