Preferential Iron Trafficking Characterizes Glioblastoma Stem-like Cells

David L. Schonberg; Tyler E. Miller; Qiulian Wu; William A. Flavahan; Nupur K. Das; James S. Hale; Christopher G. Hubert; Stephen C. Mack; Awad M. Jarrar; Robert T. Karl; Ann Mari Rosager; Anne M. Nixon; Paul J. Tesar; Petra Hamerlik; Bjarne W. Kristensen; Craig Horbinski; James R. Connor; Paul L. Fox; Justin D. Lathia; Jeremy N. Rich

doi:10.1016/j.ccell.2015.09.002

Preferential Iron Trafficking Characterizes Glioblastoma Stem-like Cells

David L. Schonberg, Tyler E. Miller, Qiulian Wu, William A. Flavahan, Nupur K. Das, James S. Hale, Christopher G. Hubert, Stephen C. Mack, Awad M. Jarrar, Robert T. Karl, Ann Mari Rosager, Anne M. Nixon, Paul J. Tesar, Petra Hamerlik, Bjarne W. Kristensen, Craig Horbinski, James R. Connor, Paul L. Fox, Justin D. Lathia, Jeremy N. Rich^*

^*Corresponding author for this work

Pathology

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

247 Scopus citations

Abstract

Glioblastomas display hierarchies with self-renewing cancer stem-like cells (CSCs). RNA sequencing and enhancer mapping revealed regulatory programs unique to CSCs causing upregulation of the iron transporter transferrin, the top differentially expressed gene compared with tissue-specific progenitors. Direct interrogation of iron uptake demonstrated that CSCs potently extract iron from the microenvironment more effectively than other tumor cells. Systematic interrogation of iron flux determined that CSCs preferentially require transferrin receptor and ferritin, two core iron regulators, to propagate and form tumors in vivo. Depleting ferritin disrupted CSC mitotic progression, through the STAT3-FoxM1 regulatory axis, revealing an iron-regulated CSC pathway. Iron is a unique, primordial metal fundamental for earliest life forms, on which CSCs have an epigenetically programmed, targetable dependence.

Original language	English (US)
Article number	2152
Pages (from-to)	441-455
Number of pages	15
Journal	Cancer cell
Volume	28
Issue number	4
DOIs	https://doi.org/10.1016/j.ccell.2015.09.002
State	Published - Oct 12 2015

ASJC Scopus subject areas

Oncology
Cancer Research
Cell Biology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1016/j.ccell.2015.09.002

Cite this

Schonberg, D. L., Miller, T. E., Wu, Q., Flavahan, W. A., Das, N. K., Hale, J. S., Hubert, C. G., Mack, S. C., Jarrar, A. M., Karl, R. T., Rosager, A. M., Nixon, A. M., Tesar, P. J., Hamerlik, P., Kristensen, B. W., Horbinski, C., Connor, J. R., Fox, P. L., Lathia, J. D., & Rich, J. N. (2015). Preferential Iron Trafficking Characterizes Glioblastoma Stem-like Cells. Cancer cell, 28(4), 441-455. Article 2152. https://doi.org/10.1016/j.ccell.2015.09.002

@article{b440396fc59244b982551cb63e3bbb2e,

title = "Preferential Iron Trafficking Characterizes Glioblastoma Stem-like Cells",

abstract = "Glioblastomas display hierarchies with self-renewing cancer stem-like cells (CSCs). RNA sequencing and enhancer mapping revealed regulatory programs unique to CSCs causing upregulation of the iron transporter transferrin, the top differentially expressed gene compared with tissue-specific progenitors. Direct interrogation of iron uptake demonstrated that CSCs potently extract iron from the microenvironment more effectively than other tumor cells. Systematic interrogation of iron flux determined that CSCs preferentially require transferrin receptor and ferritin, two core iron regulators, to propagate and form tumors in vivo. Depleting ferritin disrupted CSC mitotic progression, through the STAT3-FoxM1 regulatory axis, revealing an iron-regulated CSC pathway. Iron is a unique, primordial metal fundamental for earliest life forms, on which CSCs have an epigenetically programmed, targetable dependence.",

author = "Schonberg, {David L.} and Miller, {Tyler E.} and Qiulian Wu and Flavahan, {William A.} and Das, {Nupur K.} and Hale, {James S.} and Hubert, {Christopher G.} and Mack, {Stephen C.} and Jarrar, {Awad M.} and Karl, {Robert T.} and Rosager, {Ann Mari} and Nixon, {Anne M.} and Tesar, {Paul J.} and Petra Hamerlik and Kristensen, {Bjarne W.} and Craig Horbinski and Connor, {James R.} and Fox, {Paul L.} and Lathia, {Justin D.} and Rich, {Jeremy N.}",

note = "Publisher Copyright: {\textcopyright} 2015 Elsevier Inc.",

year = "2015",

month = oct,

day = "12",

doi = "10.1016/j.ccell.2015.09.002",

language = "English (US)",

volume = "28",

pages = "441--455",

journal = "Cancer cell",

issn = "1535-6108",

publisher = "Cell Press",

number = "4",

}

Schonberg, DL, Miller, TE, Wu, Q, Flavahan, WA, Das, NK, Hale, JS, Hubert, CG, Mack, SC, Jarrar, AM, Karl, RT, Rosager, AM, Nixon, AM, Tesar, PJ, Hamerlik, P, Kristensen, BW, Horbinski, C, Connor, JR, Fox, PL, Lathia, JD & Rich, JN 2015, 'Preferential Iron Trafficking Characterizes Glioblastoma Stem-like Cells', Cancer cell, vol. 28, no. 4, 2152, pp. 441-455. https://doi.org/10.1016/j.ccell.2015.09.002

TY - JOUR

T1 - Preferential Iron Trafficking Characterizes Glioblastoma Stem-like Cells

AU - Schonberg, David L.

AU - Miller, Tyler E.

AU - Wu, Qiulian

AU - Flavahan, William A.

AU - Das, Nupur K.

AU - Hale, James S.

AU - Hubert, Christopher G.

AU - Mack, Stephen C.

AU - Jarrar, Awad M.

AU - Karl, Robert T.

AU - Rosager, Ann Mari

AU - Nixon, Anne M.

AU - Tesar, Paul J.

AU - Hamerlik, Petra

AU - Kristensen, Bjarne W.

AU - Horbinski, Craig

AU - Connor, James R.

AU - Fox, Paul L.

AU - Lathia, Justin D.

AU - Rich, Jeremy N.

PY - 2015/10/12

Y1 - 2015/10/12

N2 - Glioblastomas display hierarchies with self-renewing cancer stem-like cells (CSCs). RNA sequencing and enhancer mapping revealed regulatory programs unique to CSCs causing upregulation of the iron transporter transferrin, the top differentially expressed gene compared with tissue-specific progenitors. Direct interrogation of iron uptake demonstrated that CSCs potently extract iron from the microenvironment more effectively than other tumor cells. Systematic interrogation of iron flux determined that CSCs preferentially require transferrin receptor and ferritin, two core iron regulators, to propagate and form tumors in vivo. Depleting ferritin disrupted CSC mitotic progression, through the STAT3-FoxM1 regulatory axis, revealing an iron-regulated CSC pathway. Iron is a unique, primordial metal fundamental for earliest life forms, on which CSCs have an epigenetically programmed, targetable dependence.

AB - Glioblastomas display hierarchies with self-renewing cancer stem-like cells (CSCs). RNA sequencing and enhancer mapping revealed regulatory programs unique to CSCs causing upregulation of the iron transporter transferrin, the top differentially expressed gene compared with tissue-specific progenitors. Direct interrogation of iron uptake demonstrated that CSCs potently extract iron from the microenvironment more effectively than other tumor cells. Systematic interrogation of iron flux determined that CSCs preferentially require transferrin receptor and ferritin, two core iron regulators, to propagate and form tumors in vivo. Depleting ferritin disrupted CSC mitotic progression, through the STAT3-FoxM1 regulatory axis, revealing an iron-regulated CSC pathway. Iron is a unique, primordial metal fundamental for earliest life forms, on which CSCs have an epigenetically programmed, targetable dependence.

UR - http://www.scopus.com/inward/record.url?scp=84944043452&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84944043452&partnerID=8YFLogxK

U2 - 10.1016/j.ccell.2015.09.002

DO - 10.1016/j.ccell.2015.09.002

M3 - Article

C2 - 26461092

AN - SCOPUS:84944043452

SN - 1535-6108

VL - 28

SP - 441

EP - 455

JO - Cancer cell

JF - Cancer cell

IS - 4

M1 - 2152

ER -

Preferential Iron Trafficking Characterizes Glioblastoma Stem-like Cells

Abstract

ASJC Scopus subject areas

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this