Aiolos promotes anchorage independence by silencing p66Shc transcription in cancer cells

Xichuan Li; Zhao Xu; Wei Du; Zhenfa Zhang; Yiliang Wei; Hao Wang; Zhiyan Zhu; Litao Qin; Lin Wang; Qing Niu; Xiulan Zhao; Luc Girard; Yimei Gong; Zhenyi Ma; Baocun Sun; Zhi Yao; John D. Minna; Lance S. Terada; Zhe Liu

doi:10.1016/j.ccr.2014.03.020

Aiolos promotes anchorage independence by silencing p66^Shc transcription in cancer cells

Xichuan Li, Zhao Xu, Wei Du, Zhenfa Zhang, Yiliang Wei, Hao Wang, Zhiyan Zhu, Litao Qin, Lin Wang, Qing Niu, Xiulan Zhao, Luc Girard, Yimei Gong, Zhenyi Ma, Baocun Sun, Zhi Yao, John D. Minna, Lance S. Terada, Zhe Liu

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

58 Scopus citations

Abstract

Anchorage of tissue cells to their physical environment is an obligate requirement for survival that is lost in mature hematopoietic and in transformed epithelial cells. Here we find that a lymphocyte lineage-restricted transcription factor, Aiolos, is frequently expressed in lung cancers and predicts markedly reduced patient survival. Aiolos decreases expression of a large set of adhesion-related genes, disrupting cell-cell and cell-matrix interactions. Aiolos also reconfigures chromatin structure within the SHC1 gene, causing isoform-specific silencing of the anchorage reporter p66^Shc and blocking anoikis invitro and invivo. In lung cancer tissues and single cells, p66^Shc expression inversely correlates with that of Aiolos. Together, these findings suggest that Aiolos functions as an epigenetic driver of lymphocyte mimicry in metastatic epithelial cancers.

Original language	English (US)
Pages (from-to)	575-589
Number of pages	15
Journal	Cancer Cell
Volume	25
Issue number	5
DOIs	https://doi.org/10.1016/j.ccr.2014.03.020
State	Published - May 12 2014

ASJC Scopus subject areas

Oncology
Cancer Research

Access to Document

10.1016/j.ccr.2014.03.020

Cite this

@article{96f4d8e778964f588fcfa7e142edd2dc,

title = "Aiolos promotes anchorage independence by silencing p66Shc transcription in cancer cells",

abstract = "Anchorage of tissue cells to their physical environment is an obligate requirement for survival that is lost in mature hematopoietic and in transformed epithelial cells. Here we find that a lymphocyte lineage-restricted transcription factor, Aiolos, is frequently expressed in lung cancers and predicts markedly reduced patient survival. Aiolos decreases expression of a large set of adhesion-related genes, disrupting cell-cell and cell-matrix interactions. Aiolos also reconfigures chromatin structure within the SHC1 gene, causing isoform-specific silencing of the anchorage reporter p66Shc and blocking anoikis invitro and invivo. In lung cancer tissues and single cells, p66Shc expression inversely correlates with that of Aiolos. Together, these findings suggest that Aiolos functions as an epigenetic driver of lymphocyte mimicry in metastatic epithelial cancers.",

author = "Xichuan Li and Zhao Xu and Wei Du and Zhenfa Zhang and Yiliang Wei and Hao Wang and Zhiyan Zhu and Litao Qin and Lin Wang and Qing Niu and Xiulan Zhao and Luc Girard and Yimei Gong and Zhenyi Ma and Baocun Sun and Zhi Yao and Minna, {John D.} and Terada, {Lance S.} and Zhe Liu",

note = "Funding Information: This work was supported by the Ministry of Science and Technology of China (grants 2014CB910100 to Z.L. and 2009CB918903 to Z.Y.), the National Natural Science Foundation of China (grants 31371295, 91019012, and 31071128 to Z.L.; 81372307 and 81071730 to Z.M.; and 81101546 to X.L.), the Tianjin Municipal Science and Technology Commission (grants 11JCZDJC19000 to Z.L., 11JCZDJC18700 to Z.M., and 13JCQNJC10300 to X.L.), the specialized Fund for the Doctoral Program of Higher Education (grant 20121202110001 to Z.L.), the China Postdoctoral Science Foundation (grant 20110490792 to X.L.), and the James M. Collins for Biomedical Research and the NIH (grants R01-HL067256 and R01-HL061897 to L.S.T. and P50-CA70907 to J.D.M.). ",

year = "2014",

month = may,

day = "12",

doi = "10.1016/j.ccr.2014.03.020",

language = "English (US)",

volume = "25",

pages = "575--589",

journal = "Cancer Cell",

issn = "1535-6108",

publisher = "Cell Press",

number = "5",

}

TY - JOUR

T1 - Aiolos promotes anchorage independence by silencing p66Shc transcription in cancer cells

AU - Li, Xichuan

AU - Xu, Zhao

AU - Du, Wei

AU - Zhang, Zhenfa

AU - Wei, Yiliang

AU - Wang, Hao

AU - Zhu, Zhiyan

AU - Qin, Litao

AU - Wang, Lin

AU - Niu, Qing

AU - Zhao, Xiulan

AU - Girard, Luc

AU - Gong, Yimei

AU - Ma, Zhenyi

AU - Sun, Baocun

AU - Yao, Zhi

AU - Minna, John D.

AU - Terada, Lance S.

AU - Liu, Zhe

N1 - Funding Information: This work was supported by the Ministry of Science and Technology of China (grants 2014CB910100 to Z.L. and 2009CB918903 to Z.Y.), the National Natural Science Foundation of China (grants 31371295, 91019012, and 31071128 to Z.L.; 81372307 and 81071730 to Z.M.; and 81101546 to X.L.), the Tianjin Municipal Science and Technology Commission (grants 11JCZDJC19000 to Z.L., 11JCZDJC18700 to Z.M., and 13JCQNJC10300 to X.L.), the specialized Fund for the Doctoral Program of Higher Education (grant 20121202110001 to Z.L.), the China Postdoctoral Science Foundation (grant 20110490792 to X.L.), and the James M. Collins for Biomedical Research and the NIH (grants R01-HL067256 and R01-HL061897 to L.S.T. and P50-CA70907 to J.D.M.).

PY - 2014/5/12

Y1 - 2014/5/12

N2 - Anchorage of tissue cells to their physical environment is an obligate requirement for survival that is lost in mature hematopoietic and in transformed epithelial cells. Here we find that a lymphocyte lineage-restricted transcription factor, Aiolos, is frequently expressed in lung cancers and predicts markedly reduced patient survival. Aiolos decreases expression of a large set of adhesion-related genes, disrupting cell-cell and cell-matrix interactions. Aiolos also reconfigures chromatin structure within the SHC1 gene, causing isoform-specific silencing of the anchorage reporter p66Shc and blocking anoikis invitro and invivo. In lung cancer tissues and single cells, p66Shc expression inversely correlates with that of Aiolos. Together, these findings suggest that Aiolos functions as an epigenetic driver of lymphocyte mimicry in metastatic epithelial cancers.

AB - Anchorage of tissue cells to their physical environment is an obligate requirement for survival that is lost in mature hematopoietic and in transformed epithelial cells. Here we find that a lymphocyte lineage-restricted transcription factor, Aiolos, is frequently expressed in lung cancers and predicts markedly reduced patient survival. Aiolos decreases expression of a large set of adhesion-related genes, disrupting cell-cell and cell-matrix interactions. Aiolos also reconfigures chromatin structure within the SHC1 gene, causing isoform-specific silencing of the anchorage reporter p66Shc and blocking anoikis invitro and invivo. In lung cancer tissues and single cells, p66Shc expression inversely correlates with that of Aiolos. Together, these findings suggest that Aiolos functions as an epigenetic driver of lymphocyte mimicry in metastatic epithelial cancers.

UR - http://www.scopus.com/inward/record.url?scp=84900312417&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84900312417&partnerID=8YFLogxK

U2 - 10.1016/j.ccr.2014.03.020

DO - 10.1016/j.ccr.2014.03.020

M3 - Article

C2 - 24823637

AN - SCOPUS:84900312417

SN - 1535-6108

VL - 25

SP - 575

EP - 589

JO - Cancer Cell

JF - Cancer Cell

IS - 5

ER -

Aiolos promotes anchorage independence by silencing p66^Shc transcription in cancer cells

Abstract

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this