A LIN28B-RAN-AURKA Signaling Network Promotes Neuroblastoma Tumorigenesis

Robert W. Schnepp; Priya Khurana; Edward F. Attiyeh; Pichai Raman; Sara E. Chodosh; Derek A. Oldridge; Maria E. Gagliardi; Karina L. Conkrite; Shahab Asgharzadeh; Robert C. Seeger; Blair B. Madison; Anil K. Rustgi; John M. Maris; Sharon J. Diskin

doi:10.1016/j.ccell.2015.09.012

A LIN28B-RAN-AURKA Signaling Network Promotes Neuroblastoma Tumorigenesis

Robert W. Schnepp, Priya Khurana, Edward F. Attiyeh, Pichai Raman, Sara E. Chodosh, Derek A. Oldridge, Maria E. Gagliardi, Karina L. Conkrite, Shahab Asgharzadeh, Robert C. Seeger, Blair B. Madison, Anil K. Rustgi, John M. Maris, Sharon J. Diskin

Division of Gastroenterology

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

77 Scopus citations

Abstract

A more complete understanding of aberrant oncogenic signaling in neuroblastoma, a malignancy of the developing sympathetic nervous system, is paramount to improving patient outcomes. Recently, we identified LIN28B as an oncogenic driver in high-risk neuroblastoma. Here, we identify the oncogene RAN as a LIN28B target and show regional gain of chromosome 12q24 as an additional somatic alteration resulting in increased RAN expression. We show that LIN28B influences RAN expression by promoting RAN Binding Protein 2 expression and by directly binding RAN mRNA. Further, we demonstrate a convergence of LIN28B and RAN signaling on Aurora kinase A activity. Collectively, these findings demonstrate that LIN28B-RAN-AURKA signaling drives neuroblastoma oncogenesis, suggesting that this pathway may be amenable to therapeutic targeting.

Original language	English
Pages (from-to)	599-609
Number of pages	11
Journal	Cancer Cell
Volume	28
Issue number	5
DOIs	https://doi.org/10.1016/j.ccell.2015.09.012
State	Published - Nov 9 2015

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Schnepp, R. W., Khurana, P., Attiyeh, E. F., Raman, P., Chodosh, S. E., Oldridge, D. A., Gagliardi, M. E., Conkrite, K. L., Asgharzadeh, S., Seeger, R. C., Madison, B. B., Rustgi, A. K., Maris, J. M., & Diskin, S. J. (2015). A LIN28B-RAN-AURKA Signaling Network Promotes Neuroblastoma Tumorigenesis. Cancer Cell, 28(5), 599-609. https://doi.org/10.1016/j.ccell.2015.09.012

Schnepp, Robert W. ; Khurana, Priya ; Attiyeh, Edward F. ; Raman, Pichai ; Chodosh, Sara E. ; Oldridge, Derek A. ; Gagliardi, Maria E. ; Conkrite, Karina L. ; Asgharzadeh, Shahab ; Seeger, Robert C. ; Madison, Blair B. ; Rustgi, Anil K. ; Maris, John M. ; Diskin, Sharon J. / A LIN28B-RAN-AURKA Signaling Network Promotes Neuroblastoma Tumorigenesis. In: Cancer Cell. 2015 ; Vol. 28, No. 5. pp. 599-609.

@article{6a855b662a3449d2bb46367b6b865ef1,

title = "A LIN28B-RAN-AURKA Signaling Network Promotes Neuroblastoma Tumorigenesis",

abstract = "A more complete understanding of aberrant oncogenic signaling in neuroblastoma, a malignancy of the developing sympathetic nervous system, is paramount to improving patient outcomes. Recently, we identified LIN28B as an oncogenic driver in high-risk neuroblastoma. Here, we identify the oncogene RAN as a LIN28B target and show regional gain of chromosome 12q24 as an additional somatic alteration resulting in increased RAN expression. We show that LIN28B influences RAN expression by promoting RAN Binding Protein 2 expression and by directly binding RAN mRNA. Further, we demonstrate a convergence of LIN28B and RAN signaling on Aurora kinase A activity. Collectively, these findings demonstrate that LIN28B-RAN-AURKA signaling drives neuroblastoma oncogenesis, suggesting that this pathway may be amenable to therapeutic targeting.",

author = "Schnepp, {Robert W.} and Priya Khurana and Attiyeh, {Edward F.} and Pichai Raman and Chodosh, {Sara E.} and Oldridge, {Derek A.} and Gagliardi, {Maria E.} and Conkrite, {Karina L.} and Shahab Asgharzadeh and Seeger, {Robert C.} and Madison, {Blair B.} and Rustgi, {Anil K.} and Maris, {John M.} and Diskin, {Sharon J.}",

note = "Funding Information: This work was supported in part by NIH grants R01-CA124709 (to J.M.M.), 1RC1MD004418-01 (to J.M.M), R00-CA151869 (to S.J.D.), T32 CA009615 (to R.W.S.), K12 HD04324 (to R.W.S.), the Giulio D{\textquoteright}Angio Endowed Chair (to J.M.M.), the Alex{\textquoteright}s Lemonade Stand Foundation (to R.W.S. and J.M.M.), Andrew{\textquoteright}s Army Foundation (to J.M.M.), the Abramson Family Cancer Research Institute (to J.M.M.), K01 DK093885 (to B.B.M.), and R01-DK 056645 (to B.B.M. and A.K.R.). Publisher Copyright: {\textcopyright} 2015 Elsevier Inc.",

year = "2015",

month = nov,

day = "9",

doi = "10.1016/j.ccell.2015.09.012",

language = "English",

volume = "28",

pages = "599--609",

journal = "Cancer Cell",

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A LIN28B-RAN-AURKA Signaling Network Promotes Neuroblastoma Tumorigenesis. / Schnepp, Robert W.; Khurana, Priya; Attiyeh, Edward F.; Raman, Pichai; Chodosh, Sara E.; Oldridge, Derek A.; Gagliardi, Maria E.; Conkrite, Karina L.; Asgharzadeh, Shahab; Seeger, Robert C.; Madison, Blair B.; Rustgi, Anil K.; Maris, John M.; Diskin, Sharon J.

In: Cancer Cell, Vol. 28, No. 5, 09.11.2015, p. 599-609.

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

TY - JOUR

T1 - A LIN28B-RAN-AURKA Signaling Network Promotes Neuroblastoma Tumorigenesis

AU - Schnepp, Robert W.

AU - Khurana, Priya

AU - Attiyeh, Edward F.

AU - Raman, Pichai

AU - Chodosh, Sara E.

AU - Oldridge, Derek A.

AU - Gagliardi, Maria E.

AU - Conkrite, Karina L.

AU - Asgharzadeh, Shahab

AU - Seeger, Robert C.

AU - Madison, Blair B.

AU - Rustgi, Anil K.

AU - Maris, John M.

AU - Diskin, Sharon J.

N1 - Funding Information: This work was supported in part by NIH grants R01-CA124709 (to J.M.M.), 1RC1MD004418-01 (to J.M.M), R00-CA151869 (to S.J.D.), T32 CA009615 (to R.W.S.), K12 HD04324 (to R.W.S.), the Giulio D’Angio Endowed Chair (to J.M.M.), the Alex’s Lemonade Stand Foundation (to R.W.S. and J.M.M.), Andrew’s Army Foundation (to J.M.M.), the Abramson Family Cancer Research Institute (to J.M.M.), K01 DK093885 (to B.B.M.), and R01-DK 056645 (to B.B.M. and A.K.R.). Publisher Copyright: © 2015 Elsevier Inc.

PY - 2015/11/9

Y1 - 2015/11/9

N2 - A more complete understanding of aberrant oncogenic signaling in neuroblastoma, a malignancy of the developing sympathetic nervous system, is paramount to improving patient outcomes. Recently, we identified LIN28B as an oncogenic driver in high-risk neuroblastoma. Here, we identify the oncogene RAN as a LIN28B target and show regional gain of chromosome 12q24 as an additional somatic alteration resulting in increased RAN expression. We show that LIN28B influences RAN expression by promoting RAN Binding Protein 2 expression and by directly binding RAN mRNA. Further, we demonstrate a convergence of LIN28B and RAN signaling on Aurora kinase A activity. Collectively, these findings demonstrate that LIN28B-RAN-AURKA signaling drives neuroblastoma oncogenesis, suggesting that this pathway may be amenable to therapeutic targeting.

AB - A more complete understanding of aberrant oncogenic signaling in neuroblastoma, a malignancy of the developing sympathetic nervous system, is paramount to improving patient outcomes. Recently, we identified LIN28B as an oncogenic driver in high-risk neuroblastoma. Here, we identify the oncogene RAN as a LIN28B target and show regional gain of chromosome 12q24 as an additional somatic alteration resulting in increased RAN expression. We show that LIN28B influences RAN expression by promoting RAN Binding Protein 2 expression and by directly binding RAN mRNA. Further, we demonstrate a convergence of LIN28B and RAN signaling on Aurora kinase A activity. Collectively, these findings demonstrate that LIN28B-RAN-AURKA signaling drives neuroblastoma oncogenesis, suggesting that this pathway may be amenable to therapeutic targeting.

UR - http://www.scopus.com/inward/record.url?scp=84946548440&partnerID=8YFLogxK

U2 - 10.1016/j.ccell.2015.09.012

DO - 10.1016/j.ccell.2015.09.012

M3 - Article

C2 - 26481147

AN - SCOPUS:84946548440

VL - 28

SP - 599

EP - 609

JO - Cancer Cell

JF - Cancer Cell

SN - 1535-6108

IS - 5

ER -

A LIN28B-RAN-AURKA Signaling Network Promotes Neuroblastoma Tumorigenesis

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