CD95 promotes metastatic spread via Sck in pancreatic ductal adenocarcinoma

M. Teodorczyk; S. Kleber; D. Wollny; J. P. Sefrin; B. Aykut; A. Mateos; P. Herhaus; I. Sancho-Martinez; O. Hill; C. Gieffers; J. Sykora; W. Weichert; C. Eisen; A. Trumpp; M. R. Sprick; F. Bergmann; T. Welsch; A. Martin-Villalba

doi:10.1038/cdd.2014.217

CD95 promotes metastatic spread via Sck in pancreatic ductal adenocarcinoma

M. Teodorczyk
, S. Kleber
, D. Wollny
, J. P. Sefrin
, B. Aykut
, A. Mateos
, P. Herhaus
, I. Sancho-Martinez
, O. Hill
, C. Gieffers
, J. Sykora
, W. Weichert
, C. Eisen
, A. Trumpp
, M. R. Sprick
, F. Bergmann
, T. Welsch
, A. Martin-Villalba

Research output: Contribution to journal › Article › peer-review

49 Scopus citations

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.

Original language	English
Pages (from-to)	1192-1202
Number of pages	11
Journal	Cell Death and Differentiation
Volume	22
Issue number	7
DOIs	https://doi.org/10.1038/cdd.2014.217
State	Published - 9 Jul 2015
Externally published	Yes

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SDG 3 Good Health and Well-being

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10.1038/cdd.2014.217

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Teodorczyk, M., Kleber, S., Wollny, D., Sefrin, J. P., Aykut, B., Mateos, A., Herhaus, P., Sancho-Martinez, I., Hill, O., Gieffers, C., Sykora, J., Weichert, W., Eisen, C., Trumpp, A., Sprick, M. R., Bergmann, F., Welsch, T., & 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

@article{10d8e51d572c444b968fbb8e103be6ea,

title = "CD95 promotes metastatic spread via Sck in pancreatic ductal adenocarcinoma",

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.",

author = "M. Teodorczyk and S. Kleber and D. Wollny and Sefrin, \{J. P.\} and B. Aykut and A. Mateos and P. Herhaus and I. Sancho-Martinez and O. Hill and C. Gieffers and J. Sykora and W. Weichert and C. Eisen and A. Trumpp and Sprick, \{M. R.\} and F. Bergmann and T. Welsch and A. Martin-Villalba",

year = "2015",

month = jul,

day = "9",

doi = "10.1038/cdd.2014.217",

language = "English",

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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 2015, 'CD95 promotes metastatic spread via Sck in pancreatic ductal adenocarcinoma', Cell Death and Differentiation, vol. 22, no. 7, pp. 1192-1202. https://doi.org/10.1038/cdd.2014.217

TY - JOUR

T1 - CD95 promotes metastatic spread via Sck in pancreatic ductal adenocarcinoma

AU - Teodorczyk, M.

AU - Kleber, S.

AU - Wollny, D.

AU - Sefrin, J. P.

AU - Aykut, B.

AU - Mateos, A.

AU - Herhaus, P.

AU - Sancho-Martinez, I.

AU - Hill, O.

AU - Gieffers, C.

AU - Sykora, J.

AU - Weichert, W.

AU - Eisen, C.

AU - Trumpp, A.

AU - Sprick, M. R.

AU - Bergmann, F.

AU - Welsch, T.

AU - Martin-Villalba, A.

PY - 2015/7/9

Y1 - 2015/7/9

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/84930753559

U2 - 10.1038/cdd.2014.217

DO - 10.1038/cdd.2014.217

M3 - Article

C2 - 25613377

AN - SCOPUS:84930753559

SN - 1350-9047

VL - 22

SP - 1192

EP - 1202

JO - Cell Death and Differentiation

JF - Cell Death and Differentiation

IS - 7

ER -

CD95 promotes metastatic spread via Sck in pancreatic ductal adenocarcinoma

Abstract

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