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CD95 promotes metastatic spread via Sck in pancreatic ductal adenocarcinoma.

Publication ,  Journal Article
Teodorczyk, M; Kleber, S; Wollny, D; Sefrin, JP; Aykut, B; Mateos, A; Herhaus, P; Sancho-Martinez, I; Hill, O; Gieffers, C; Sykora, J ...
Published in: Cell death and differentiation
July 2015
Published version (DOI) Open Access Copy (Duke)

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.

Duke Scholars

Berk Aykut
Author Berk Aykut  

Published In

Cell death and differentiation

DOI

10.1038/cdd.2014.217

EISSN

1476-5403

ISSN

1350-9047

Publication Date

July 2015

Volume

22

Issue

7

Start / End Page

1192 / 1202

Related Subject Headings

  • fas Receptor
  • Xenograft Model Antitumor Assays
  • Src Homology 2 Domain-Containing, Transforming Protein 2
  • Signal Transduction
  • Shc Signaling Adaptor Proteins
  • Pancreatic Neoplasms
  • Neoplasm Metastasis
  • Mice
  • Humans
  • Female
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Teodorczyk, M., Kleber, S., Wollny, D., Sefrin, J. P., Aykut, B., Mateos, A., … Martin-Villalba, A. (2015). CD95 promotes metastatic spread via Sck in pancreatic ductal adenocarcinoma. Cell Death and Differentiation, 22(7), 1192–1202. https://doi.org/10.1038/cdd.2014.217
Teodorczyk, M., S. Kleber, D. Wollny, J. P. Sefrin, B. Aykut, A. Mateos, P. Herhaus, et al. “CD95 promotes metastatic spread via Sck in pancreatic ductal adenocarcinoma.” Cell Death and Differentiation 22, no. 7 (July 2015): 1192–1202. https://doi.org/10.1038/cdd.2014.217.
Teodorczyk M, Kleber S, Wollny D, Sefrin JP, Aykut B, Mateos A, et al. CD95 promotes metastatic spread via Sck in pancreatic ductal adenocarcinoma. Cell death and differentiation. 2015 Jul;22(7):1192–202.
Teodorczyk, M., et al. “CD95 promotes metastatic spread via Sck in pancreatic ductal adenocarcinoma.” Cell Death and Differentiation, vol. 22, no. 7, July 2015, pp. 1192–202. Epmc, doi:10.1038/cdd.2014.217.
Teodorczyk M, Kleber S, Wollny D, Sefrin JP, Aykut B, Mateos A, Herhaus P, Sancho-Martinez I, Hill O, Gieffers C, Sykora J, Weichert W, Eisen C, Trumpp A, Sprick MR, Bergmann F, Welsch T, Martin-Villalba A. CD95 promotes metastatic spread via Sck in pancreatic ductal adenocarcinoma. Cell death and differentiation. 2015 Jul;22(7):1192–1202.

Published In

Cell death and differentiation

DOI

10.1038/cdd.2014.217

EISSN

1476-5403

ISSN

1350-9047

Publication Date

July 2015

Volume

22

Issue

7

Start / End Page

1192 / 1202

Related Subject Headings

  • fas Receptor
  • Xenograft Model Antitumor Assays
  • Src Homology 2 Domain-Containing, Transforming Protein 2
  • Signal Transduction
  • Shc Signaling Adaptor Proteins
  • Pancreatic Neoplasms
  • Neoplasm Metastasis
  • Mice
  • Humans
  • Female