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 p66Shc transcription in cancer cells

Cancer Cell. 2014 May 12;25(5):575-89. doi: 10.1016/j.ccr.2014.03.020.

Authors

Xichuan Li¹, Zhao Xu², Wei Du¹, Zhenfa Zhang³, Yiliang Wei¹, Hao Wang¹, Zhiyan Zhu¹, Litao Qin¹, Lin Wang¹, Qing Niu¹, Xiulan Zhao⁴, Luc Girard⁵, Yimei Gong⁶, Zhenyi Ma⁷, Baocun Sun⁴, Zhi Yao⁸, John D Minna⁵, Lance S Terada⁹, Zhe Liu¹⁰

Affiliations

¹ Department of Immunology, Biochemistry and Molecular Biology, 2011 Collaborative Innovation Center of Tianjin for Medical Epigenetics, Tianjin Key Laboratory of Medical Epigenetics, Tianjin Medical University, Tianjin 300070, China; Laboratory of Epigenetics and Tumorigenesis, Tianjin Research Center of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China.
² Department of Immunology, Biochemistry and Molecular Biology, 2011 Collaborative Innovation Center of Tianjin for Medical Epigenetics, Tianjin Key Laboratory of Medical Epigenetics, Tianjin Medical University, Tianjin 300070, China; Laboratory of Epigenetics and Tumorigenesis, Tianjin Research Center of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China; Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, Tianjin 300211, China.
³ Department of Lung Cancer Center, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060, China.
⁴ Department of Pathology, Tianjin Medical University, Tianjin 300070, China.
⁵ Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA.
⁶ Division of Pulmonary and Critical Care, Department of Internal Medicine, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA.
⁷ Department of Immunology, Biochemistry and Molecular Biology, 2011 Collaborative Innovation Center of Tianjin for Medical Epigenetics, Tianjin Key Laboratory of Medical Epigenetics, Tianjin Medical University, Tianjin 300070, China.
⁸ Department of Immunology, Biochemistry and Molecular Biology, 2011 Collaborative Innovation Center of Tianjin for Medical Epigenetics, Tianjin Key Laboratory of Medical Epigenetics, Tianjin Medical University, Tianjin 300070, China; Key Laboratory of Immune Microenvironment and Disease of the Ministry of Education, Tianjin Medical University, Tianjin 300070, China.
⁹ Division of Pulmonary and Critical Care, Department of Internal Medicine, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA. Electronic address: lance.terada@utsouthwestern.edu.
¹⁰ Department of Immunology, Biochemistry and Molecular Biology, 2011 Collaborative Innovation Center of Tianjin for Medical Epigenetics, Tianjin Key Laboratory of Medical Epigenetics, Tianjin Medical University, Tianjin 300070, China; Key Laboratory of Immune Microenvironment and Disease of the Ministry of Education, Tianjin Medical University, Tianjin 300070, China; Laboratory of Epigenetics and Tumorigenesis, Tianjin Research Center of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China. Electronic address: zheliu@tmu.edu.cn.

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 in vitro and in vivo. 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.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Anoikis / genetics
Carcinoma, Non-Small-Cell Lung / genetics*
Carcinoma, Non-Small-Cell Lung / metabolism
Carcinoma, Non-Small-Cell Lung / mortality
Cell Adhesion / genetics
Cell Adhesion / physiology
Cell Communication / physiology
Cell Line, Tumor
Cell Proliferation
Cell Transformation, Neoplastic / genetics
Chromatin / metabolism
Gene Expression Profiling
Gene Expression Regulation, Neoplastic*
Gene Silencing*
Humans
Ikaros Transcription Factor / metabolism*
Lung / metabolism
Lung / pathology
Lung Neoplasms / genetics*
Lung Neoplasms / metabolism
Lung Neoplasms / mortality
Lymphopoiesis / genetics
Promoter Regions, Genetic
Shc Signaling Adaptor Proteins / genetics*
Src Homology 2 Domain-Containing, Transforming Protein 1
Transcription, Genetic

Substances

Chromatin
IKZF3 protein, human
SHC1 protein, human
Shc Signaling Adaptor Proteins
Src Homology 2 Domain-Containing, Transforming Protein 1
Ikaros Transcription Factor

Associated data

GEO/GSE50812

Abstract

Publication types

MeSH terms

Substances

Associated data

Grants and funding