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Cell Death Differ. 2015 Jul;22(7):1192-202. doi: 10.1038/cdd.2014.217. Epub 2015 Jan 23.

CD95 promotes metastatic spread via Sck in pancreatic ductal adenocarcinoma.

Author information

1
Molecular Neurobiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
2
Apogenix GmbH, Heidelberg, Germany.
3
Institute of Pathology, University of Heidelberg, Heidelberg, Germany.
4
1] Division of Stem Cells and Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany [2] Heidelberg Institute for Stem Cell Technology and Experimental Medicine gGmbH, Heidelberg, Germany.
5
1] Division of Stem Cells and Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany [2] Heidelberg Institute for Stem Cell Technology and Experimental Medicine gGmbH, Heidelberg, Germany [3] German Cancer Consortium (DKTK), Heidelberg, Germany.
6
Department of General, Visceral and Transplantation Surgery, Heidelberg, Germany.

Abstract

Cancer stem cells (CSCs) have been implicated in the initiation and maintenance of tumour growth as well as metastasis. Recent reports link stemness to epithelial-mesenchymal transition (EMT) in cancer. However, there is still little knowledge about the molecular markers of those events. In silico analysis of RNA profiles of 36 pancreatic ductal adenocarcinomas (PDAC) reveals an association of the expression of CD95 with EMT and stemness that was validated in CSCs isolated from PDAC surgical specimens. CD95 expression was also higher in metastatic pancreatic cells than in primary PDAC. Pharmacological inhibition of CD95 activity reduced PDAC growth and metastasis in CSC-derived xenografts and in a murine syngeneic model. On the mechanistic level, Sck was identified as a novel molecule indispensable for CD95's induction of cell cycle progression. This study uncovers CD95 as a marker of EMT and stemness in PDAC. It also addresses the molecular mechanism by which CD95 drives tumour growth and opens tantalizing therapeutic possibilities in PDAC.

PMID:
25613377
PMCID:
PMC4572867
DOI:
10.1038/cdd.2014.217
[Indexed for MEDLINE]
Free PMC Article

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