Aiolos promotes anchorage independence by silencing p66Shc transcription in cancer cells.
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.
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.
Xichuan
X
Li
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.
Zhao
Z
Xu
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.
Wei
W
Du
Department of Lung Cancer Center, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060, China.
Zhenfa
Z
Zhang
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.
Yiliang
Y
Wei
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.
Hao
H
Wang
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.
Zhiyan
Z
Zhu
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.
Litao
L
Qin
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.
Lin
L
Wang
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.
Qing
Q
Niu
Department of Pathology, Tianjin Medical University, Tianjin 300070, China.
Xiulan
X
Zhao
Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA.
Luc
L
Girard
Division of Pulmonary and Critical Care, Department of Internal Medicine, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA.
Yimei
Y
Gong
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.
Zhenyi
Z
Ma
Department of Pathology, Tianjin Medical University, Tianjin 300070, China.
Baocun
B
Sun
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.
Zhi
Z
Yao
Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA.
John D
JD
Minna
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.
Lance S
LS
Terada
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.
Zhe
Z
Liu
D023102:Anoikis / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000378:metabolism / Q000401:mortality; D002448:Cell Adhesion / Q000235:genetics / Q000502:physiology; D002450:Cell Communication / Q000502:physiology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D002843:Chromatin / Q000378:metabolism; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006801:Humans; D051740:Ikaros Transcription Factor / Q000378:metabolism*; D008168:Lung / Q000378:metabolism / Q000473:pathology; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000401:mortality; D038041:Lymphopoiesis / Q000235:genetics; D011401:Promoter Regions, Genetic; D055765:Shc Signaling Adaptor Proteins / Q000235:genetics*; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1; D014158:Transcription, Genetic
D002843:Chromatin; C106285:IKZF3 protein, human; C528024:SHC1 protein, human; D055765:Shc Signaling Adaptor Proteins; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1; D051740:Ikaros Transcription Factor