CD95/Fas Increases Stemness in Cancer Cells by Inducing a STAT1-Dependent Type I Interferon Response

Abdul S. Qadir; Paolo Ceppi; Sonia Brockway; Calvin Law; Liang Mu; Nikolai N. Khodarev; Jung Kim; Jonathan C. Zhao; William Putzbach; Andrea E. Murmann; Zhuo Chen; Wenjing Chen; Xia Liu; Arthur R. Salomon; Huiping Liu; Ralph R. Weichselbaum; Jindan Yu; Marcus E. Peter

doi:10.1016/j.celrep.2017.02.037

CD95/Fas Increases Stemness in Cancer Cells by Inducing a STAT1-Dependent Type I Interferon Response

Abdul S. Qadir
, Paolo Ceppi
, Sonia Brockway
, Calvin Law
, Liang Mu
, Nikolai N. Khodarev
, Jung Kim
, Jonathan C. Zhao
, William Putzbach
, Andrea E. Murmann
, Zhuo Chen
, Wenjing Chen
, Xia Liu
, Arthur R. Salomon
, Huiping Liu
, Ralph R. Weichselbaum
, Jindan Yu
, Marcus E. Peter

Producción científica: Article › revisión exhaustiva

92 Citas (Scopus)

Resumen

Stimulation of CD95/Fas drives and maintains cancer stem cells (CSCs). We now report that this involves activation of signal transducer and activator of transcription 1 (STAT1) and induction of STAT1-regulated genes and that this process is inhibited by active caspases. STAT1 is enriched in CSCs in cancer cell lines, patient-derived human breast cancer, and CD95^high-expressing glioblastoma neurospheres. CD95 stimulation of cancer cells induced secretion of type I interferons (IFNs) that bind to type I IFN receptors, resulting in activation of Janus-activated kinases, activation of STAT1, and induction of a number of STAT1-regulated genes that are part of a gene signature recently linked to therapy resistance in five primary human cancers. Consequently, we identified type I IFNs as drivers of cancer stemness. Knockdown or knockout of STAT1 resulted in a strongly reduced ability of CD95L or type I IFN to increase cancer stemness. This identifies STAT1 as a key regulator of the CSC-inducing activity of CD95.

Idioma original	English
Páginas (desde-hasta)	2373-2386
Número de páginas	14
Publicación	Cell Reports
Volumen	18
N.º	10
DOI	https://doi.org/10.1016/j.celrep.2017.02.037
Estado	Published - mar 7 2017

Nota bibliográfica

Publisher Copyright:
© 2017 The Author(s)

Financiación

We are grateful to Denise Scholten for performing the gene set enrichment analysis and to Drs. Platanias and Horvath for helpful discussions. We would like to thank Dr. Youjia Hua for analyzing the Illumina gene array data, Dr. Yingming Zhao for assessing the labeling efficiency of the cells used in the SILAC experiment, and Angel Alvarez for providing the GSC20 cells. This work was funded by DOD postdoctoral fellowships W81XWH-13-1-0301 (to P.C.), R00CA160638 and ACS127951-RSG-15-025-01-CS (to H.L.), and a Northwestern Memorial Foundation-Lynn Sage Cancer Research Foundation grant R01CA149356, and R35CA197450 (to M.E.P.).

Financiadores	Número del financiador
Northwestern Memorial Foundation-Lynn Sage Cancer Research Foundation	R35CA197450
U.S. Department of Defense	ACS127951-RSG-15-025-01-CS, W81XWH-13-1-0301, R00CA160638
U.S. Department of Defense
National Childhood Cancer Registry – National Cancer Institute	R01CA149356
National Childhood Cancer Registry – National Cancer Institute

ODS de las Naciones Unidas

Este resultado contribuye a los siguientes Objetivos de Desarrollo Sostenible

Good health and well being

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

Acceder al documento

10.1016/j.celrep.2017.02.037

Otros archivos y enlaces

Citar esto

Qadir, A. S., Ceppi, P., Brockway, S., Law, C., Mu, L., Khodarev, N. N., Kim, J., Zhao, J. C., Putzbach, W., Murmann, A. E., Chen, Z., Chen, W., Liu, X., Salomon, A. R., Liu, H., Weichselbaum, R. R., Yu, J., & Peter, M. E. (2017). CD95/Fas Increases Stemness in Cancer Cells by Inducing a STAT1-Dependent Type I Interferon Response. Cell Reports, 18(10), 2373-2386. https://doi.org/10.1016/j.celrep.2017.02.037

@article{f5403ec7f71b4724a04195c96545bbf5,

title = "CD95/Fas Increases Stemness in Cancer Cells by Inducing a STAT1-Dependent Type I Interferon Response",

abstract = "Stimulation of CD95/Fas drives and maintains cancer stem cells (CSCs). We now report that this involves activation of signal transducer and activator of transcription 1 (STAT1) and induction of STAT1-regulated genes and that this process is inhibited by active caspases. STAT1 is enriched in CSCs in cancer cell lines, patient-derived human breast cancer, and CD95high-expressing glioblastoma neurospheres. CD95 stimulation of cancer cells induced secretion of type I interferons (IFNs) that bind to type I IFN receptors, resulting in activation of Janus-activated kinases, activation of STAT1, and induction of a number of STAT1-regulated genes that are part of a gene signature recently linked to therapy resistance in five primary human cancers. Consequently, we identified type I IFNs as drivers of cancer stemness. Knockdown or knockout of STAT1 resulted in a strongly reduced ability of CD95L or type I IFN to increase cancer stemness. This identifies STAT1 as a key regulator of the CSC-inducing activity of CD95.",

keywords = "Fas, STAT1, breast cancer, cancer stem cells, head and neck cancer, type I interferons",

author = "Qadir, \{Abdul S.\} and Paolo Ceppi and Sonia Brockway and Calvin Law and Liang Mu and Khodarev, \{Nikolai N.\} and Jung Kim and Zhao, \{Jonathan C.\} and William Putzbach and Murmann, \{Andrea E.\} and Zhuo Chen and Wenjing Chen and Xia Liu and Salomon, \{Arthur R.\} and Huiping Liu and Weichselbaum, \{Ralph R.\} and Jindan Yu and Peter, \{Marcus E.\}",

note = "Publisher Copyright: {\textcopyright} 2017 The Author(s)",

year = "2017",

month = mar,

day = "7",

doi = "10.1016/j.celrep.2017.02.037",

language = "English",

volume = "18",

pages = "2373--2386",

number = "10",

}

Qadir, AS, Ceppi, P, Brockway, S, Law, C, Mu, L, Khodarev, NN, Kim, J, Zhao, JC, Putzbach, W, Murmann, AE, Chen, Z, Chen, W, Liu, X, Salomon, AR, Liu, H, Weichselbaum, RR, Yu, J & Peter, ME 2017, 'CD95/Fas Increases Stemness in Cancer Cells by Inducing a STAT1-Dependent Type I Interferon Response', Cell Reports, vol. 18, n.º 10, pp. 2373-2386. https://doi.org/10.1016/j.celrep.2017.02.037

TY - JOUR

T1 - CD95/Fas Increases Stemness in Cancer Cells by Inducing a STAT1-Dependent Type I Interferon Response

AU - Qadir, Abdul S.

AU - Ceppi, Paolo

AU - Brockway, Sonia

AU - Law, Calvin

AU - Mu, Liang

AU - Khodarev, Nikolai N.

AU - Kim, Jung

AU - Zhao, Jonathan C.

AU - Putzbach, William

AU - Murmann, Andrea E.

AU - Chen, Zhuo

AU - Chen, Wenjing

AU - Liu, Xia

AU - Salomon, Arthur R.

AU - Liu, Huiping

AU - Weichselbaum, Ralph R.

AU - Yu, Jindan

AU - Peter, Marcus E.

PY - 2017/3/7

Y1 - 2017/3/7

N2 - Stimulation of CD95/Fas drives and maintains cancer stem cells (CSCs). We now report that this involves activation of signal transducer and activator of transcription 1 (STAT1) and induction of STAT1-regulated genes and that this process is inhibited by active caspases. STAT1 is enriched in CSCs in cancer cell lines, patient-derived human breast cancer, and CD95high-expressing glioblastoma neurospheres. CD95 stimulation of cancer cells induced secretion of type I interferons (IFNs) that bind to type I IFN receptors, resulting in activation of Janus-activated kinases, activation of STAT1, and induction of a number of STAT1-regulated genes that are part of a gene signature recently linked to therapy resistance in five primary human cancers. Consequently, we identified type I IFNs as drivers of cancer stemness. Knockdown or knockout of STAT1 resulted in a strongly reduced ability of CD95L or type I IFN to increase cancer stemness. This identifies STAT1 as a key regulator of the CSC-inducing activity of CD95.

AB - Stimulation of CD95/Fas drives and maintains cancer stem cells (CSCs). We now report that this involves activation of signal transducer and activator of transcription 1 (STAT1) and induction of STAT1-regulated genes and that this process is inhibited by active caspases. STAT1 is enriched in CSCs in cancer cell lines, patient-derived human breast cancer, and CD95high-expressing glioblastoma neurospheres. CD95 stimulation of cancer cells induced secretion of type I interferons (IFNs) that bind to type I IFN receptors, resulting in activation of Janus-activated kinases, activation of STAT1, and induction of a number of STAT1-regulated genes that are part of a gene signature recently linked to therapy resistance in five primary human cancers. Consequently, we identified type I IFNs as drivers of cancer stemness. Knockdown or knockout of STAT1 resulted in a strongly reduced ability of CD95L or type I IFN to increase cancer stemness. This identifies STAT1 as a key regulator of the CSC-inducing activity of CD95.

KW - Fas

KW - STAT1

KW - breast cancer

KW - cancer stem cells

KW - head and neck cancer

KW - type I interferons

UR - https://www.scopus.com/pages/publications/85014578201

UR - https://www.scopus.com/pages/publications/85014578201#tab=citedBy

U2 - 10.1016/j.celrep.2017.02.037

DO - 10.1016/j.celrep.2017.02.037

M3 - Article

C2 - 28273453

AN - SCOPUS:85014578201

SN - 2211-1247

VL - 18

SP - 2373

EP - 2386

JO - Cell Reports

JF - Cell Reports

IS - 10

ER -

CD95/Fas Increases Stemness in Cancer Cells by Inducing a STAT1-Dependent Type I Interferon Response

Resumen

Nota bibliográfica

Financiación

ODS de las Naciones Unidas

ASJC Scopus subject areas

Acceder al documento

Otros archivos y enlaces

Huella

Citar esto