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

Research output: Contribution to journalArticle

39 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 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.

Original languageEnglish (US)
Pages (from-to)575-589
Number of pages15
JournalCancer Cell
Volume25
Issue number5
DOIs
StatePublished - May 12 2014

ASJC Scopus subject areas

  • Oncology
  • Cell Biology
  • Cancer Research

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