American Association for Cancer Research
Browse
00085472can181234-sup-200662_4_supp_5194718_pjy19n.docx (62.9 kB)

Supplementary Data from p53-Suppressed Oncogene TET1 Prevents Cellular Aging in Lung Cancer

Download (62.9 kB)
journal contribution
posted on 2023-03-31, 03:05 authored by Piotr T. Filipczak, Shuguang Leng, Carmen S. Tellez, Kieu C. Do, Marcie J. Grimes, Cynthia L. Thomas, Stephanie R. Walton-Filipczak, Maria A. Picchi, Steven A. Belinsky

Supplementary methods, figure legends and tables

Funding

NIH

History

ARTICLE ABSTRACT

The role of transcriptional regulator ten-eleven translocation methylcytosine dioxygenease 1 (TET1) has not been well characterized in lung cancer. Here we show that TET1 is overexpressed in adenocarcinoma and squamous cell carcinomas. TET1 knockdown reduced cell growth in vitro and in vivo and induced transcriptome reprogramming independent of its demethylating activity to affect key cancer signaling pathways. Wild-type p53 bound the TET1 promoter to suppress transcription, while p53 transversion mutations were most strongly associated with high TET1 expression. Knockdown of TET1 in p53-mutant cell lines induced senescence through a program involving generalized genomic instability manifested by DNA single- and double-strand breaks and induction of p21 that was synergistic with cisplatin and doxorubicin. These data identify TET1 as an oncogene in lung cancer whose gain of function via loss of p53 may be exploited through targeted therapy–induced senescence. These studies identify TET1 as an oncogene in lung cancer whose gain of function following loss of p53 may be exploited by targeted therapy–induced senescence.See related commentary by Kondo, p. 1751

Usage metrics

    Cancer Research

    Licence

    Exports

    RefWorks
    BibTeX
    Ref. manager
    Endnote
    DataCite
    NLM
    DC