ARS2/MAGL signaling in glioblastoma stem cells promotes self-renewal and M2-like polarization of tumor-associated macrophages

Jinlong Yin; Sung Soo Kim; Eunji  Choi; Young Taek Oh; Weiwei  Lin; Tae-Hoon Kim; Jason K. Sa; Jun Hee Hong; Se Hwan Park; Hyung Joon Kwon; Xiong  Jin; Yeonhee  You; Ji Hye Kim; Hyunggee  Kim; Jaekyoung  Son; Jeongwu  Lee; Do-Hyun  Nam; Kui Son Choi; Bingyang Shi; Ho-Shin  Gwak; Heon  Yoo; Antonio  Iavarone; Jong Heon Kim; Jong Bae Park

doi:10.1038/s41467-020-16789-2

ARS2/MAGL signaling in glioblastoma stem cells promotes self-renewal and M2-like polarization of tumor-associated macrophages

Jinlong Yin^*, Sung Soo Kim, Eunji Choi, Young Taek Oh, Weiwei Lin, Tae-Hoon Kim, Jason K. Sa, Jun Hee Hong, Se Hwan Park, Hyung Joon Kwon, Xiong Jin, Yeonhee You, Ji Hye Kim, Hyunggee Kim, Jaekyoung Son, Jeongwu Lee, Do-Hyun Nam, Kui Son Choi, Bingyang Shi, Ho-Shin GwakHeon Yoo, Antonio Iavarone, Jong Heon Kim, Jong Bae Park

^*Corresponding author for this work

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

90 Citations (Scopus)

78 Downloads (Pure)

Abstract

The interplay between glioblastoma stem cells (GSCs) and tumor-associated macrophages (TAMs) promotes progression of glioblastoma multiforme (GBM). However, the detailed molecular mechanisms underlying the relationship between these two cell types remain unclear. Here, we demonstrate that ARS2 (arsenite-resistance protein 2), a zinc finger protein that is essential for early mammalian development, plays critical roles in GSC maintenance and M2-like TAM polarization. ARS2 directly activates its novel transcriptional target MGLL, encoding monoacylglycerol lipase (MAGL), to regulate the self-renewal and tumorigenicity of GSCs through production of prostaglandin E2 (PGE2), which stimulates β-catenin activation of GSC and M2-like TAM polarization. We identify M2-like signature downregulated by which MAGL-specific inhibitor, JZL184, increased survival rate significantly in the mouse xenograft model by blocking PGE2 production. Taken together, our results suggest that blocking the interplay between GSCs and TAMs by targeting ARS2/MAGL signaling offers a potentially novel therapeutic option for GBM patients.

Original language	English
Article number	2978
Pages (from-to)	1-15
Number of pages	15
Journal	Nature Communications
Volume	11
DOIs	https://doi.org/10.1038/s41467-020-16789-2
Publication status	Published - 12 Jun 2020

Bibliographical note

Copyright the Author(s) 2020. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

Access to Document

10.1038/s41467-020-16789-2Licence: CC BY

Publisher version (open access)Final published version, 4.1 MBLicence: CC BY

Cite this

Yin, J., Kim, S. S., Choi, E., Oh, Y. T., Lin, W., Kim, T-H., Sa, J. K., Hong, J. H., Park, S. H., Kwon, H. J., Jin, X., You, Y., Kim, J. H., Kim, H., Son, J., Lee, J., Nam, D-H., Choi, K. S., Shi, B., ... Park, J. B. (2020). ARS2/MAGL signaling in glioblastoma stem cells promotes self-renewal and M2-like polarization of tumor-associated macrophages. Nature Communications, 11, 1-15. [2978]. https://doi.org/10.1038/s41467-020-16789-2

@article{14f22dc8b8914d9ab72531c5f91e76fb,

title = "ARS2/MAGL signaling in glioblastoma stem cells promotes self-renewal and M2-like polarization of tumor-associated macrophages",

abstract = "The interplay between glioblastoma stem cells (GSCs) and tumor-associated macrophages (TAMs) promotes progression of glioblastoma multiforme (GBM). However, the detailed molecular mechanisms underlying the relationship between these two cell types remain unclear. Here, we demonstrate that ARS2 (arsenite-resistance protein 2), a zinc finger protein that is essential for early mammalian development, plays critical roles in GSC maintenance and M2-like TAM polarization. ARS2 directly activates its novel transcriptional target MGLL, encoding monoacylglycerol lipase (MAGL), to regulate the self-renewal and tumorigenicity of GSCs through production of prostaglandin E2 (PGE2), which stimulates β-catenin activation of GSC and M2-like TAM polarization. We identify M2-like signature downregulated by which MAGL-specific inhibitor, JZL184, increased survival rate significantly in the mouse xenograft model by blocking PGE2 production. Taken together, our results suggest that blocking the interplay between GSCs and TAMs by targeting ARS2/MAGL signaling offers a potentially novel therapeutic option for GBM patients.",

author = "Jinlong Yin and Kim, {Sung Soo} and Eunji Choi and Oh, {Young Taek} and Weiwei Lin and Tae-Hoon Kim and Sa, {Jason K.} and Hong, {Jun Hee} and Park, {Se Hwan} and Kwon, {Hyung Joon} and Xiong Jin and Yeonhee You and Kim, {Ji Hye} and Hyunggee Kim and Jaekyoung Son and Jeongwu Lee and Do-Hyun Nam and Choi, {Kui Son} and Bingyang Shi and Ho-Shin Gwak and Heon Yoo and Antonio Iavarone and Kim, {Jong Heon} and Park, {Jong Bae}",

note = "Copyright the Author(s) 2020. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.",

year = "2020",

month = jun,

day = "12",

doi = "10.1038/s41467-020-16789-2",

language = "English",

volume = "11",

pages = "1--15",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Springer, Springer Nature",

}

Yin, J, Kim, SS, Choi, E, Oh, YT, Lin, W, Kim, T-H, Sa, JK, Hong, JH, Park, SH, Kwon, HJ, Jin, X, You, Y, Kim, JH, Kim, H, Son, J, Lee, J, Nam, D-H, Choi, KS, Shi, B, Gwak, H-S, Yoo, H, Iavarone, A, Kim, JH & Park, JB 2020, 'ARS2/MAGL signaling in glioblastoma stem cells promotes self-renewal and M2-like polarization of tumor-associated macrophages', Nature Communications, vol. 11, 2978, pp. 1-15. https://doi.org/10.1038/s41467-020-16789-2

TY - JOUR

T1 - ARS2/MAGL signaling in glioblastoma stem cells promotes self-renewal and M2-like polarization of tumor-associated macrophages

AU - Yin, Jinlong

AU - Kim, Sung Soo

AU - Choi, Eunji

AU - Oh, Young Taek

AU - Lin, Weiwei

AU - Kim, Tae-Hoon

AU - Sa, Jason K.

AU - Hong, Jun Hee

AU - Park, Se Hwan

AU - Kwon, Hyung Joon

AU - Jin, Xiong

AU - You, Yeonhee

AU - Kim, Ji Hye

AU - Kim, Hyunggee

AU - Son, Jaekyoung

AU - Lee, Jeongwu

AU - Nam, Do-Hyun

AU - Choi, Kui Son

AU - Shi, Bingyang

AU - Gwak, Ho-Shin

AU - Yoo, Heon

AU - Iavarone, Antonio

AU - Kim, Jong Heon

AU - Park, Jong Bae

N1 - Copyright the Author(s) 2020. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

PY - 2020/6/12

Y1 - 2020/6/12

N2 - The interplay between glioblastoma stem cells (GSCs) and tumor-associated macrophages (TAMs) promotes progression of glioblastoma multiforme (GBM). However, the detailed molecular mechanisms underlying the relationship between these two cell types remain unclear. Here, we demonstrate that ARS2 (arsenite-resistance protein 2), a zinc finger protein that is essential for early mammalian development, plays critical roles in GSC maintenance and M2-like TAM polarization. ARS2 directly activates its novel transcriptional target MGLL, encoding monoacylglycerol lipase (MAGL), to regulate the self-renewal and tumorigenicity of GSCs through production of prostaglandin E2 (PGE2), which stimulates β-catenin activation of GSC and M2-like TAM polarization. We identify M2-like signature downregulated by which MAGL-specific inhibitor, JZL184, increased survival rate significantly in the mouse xenograft model by blocking PGE2 production. Taken together, our results suggest that blocking the interplay between GSCs and TAMs by targeting ARS2/MAGL signaling offers a potentially novel therapeutic option for GBM patients.

AB - The interplay between glioblastoma stem cells (GSCs) and tumor-associated macrophages (TAMs) promotes progression of glioblastoma multiforme (GBM). However, the detailed molecular mechanisms underlying the relationship between these two cell types remain unclear. Here, we demonstrate that ARS2 (arsenite-resistance protein 2), a zinc finger protein that is essential for early mammalian development, plays critical roles in GSC maintenance and M2-like TAM polarization. ARS2 directly activates its novel transcriptional target MGLL, encoding monoacylglycerol lipase (MAGL), to regulate the self-renewal and tumorigenicity of GSCs through production of prostaglandin E2 (PGE2), which stimulates β-catenin activation of GSC and M2-like TAM polarization. We identify M2-like signature downregulated by which MAGL-specific inhibitor, JZL184, increased survival rate significantly in the mouse xenograft model by blocking PGE2 production. Taken together, our results suggest that blocking the interplay between GSCs and TAMs by targeting ARS2/MAGL signaling offers a potentially novel therapeutic option for GBM patients.

UR - http://www.scopus.com/inward/record.url?scp=85086322411&partnerID=8YFLogxK

U2 - 10.1038/s41467-020-16789-2

DO - 10.1038/s41467-020-16789-2

M3 - Article

C2 - 32532977

SN - 2041-1723

VL - 11

SP - 1

EP - 15

JO - Nature Communications

JF - Nature Communications

M1 - 2978

ER -

ARS2/MAGL signaling in glioblastoma stem cells promotes self-renewal and M2-like polarization of tumor-associated macrophages

Abstract

Bibliographical note

Access to Document

Other files and links

Fingerprint

Cite this