XPO7 is a tumor suppressor regulating p21CIP1-dependent senescence

Senescence is a key barrier to neoplastic transformation. To identify senescence regulators relevant to cancer, we screened a genome-wide shRNA library. Here, we describe exportin 7 (XPO7) as a novel regulator of senescence and validate its function in telomere-induced, replicative, and oncogene-ind...

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Bibliographic Details
Published in:Genes & development 2021-03, Vol.35 (5-6), p.379-391
Main Authors: Innes, Andrew J, Sun, Bin, Wagner, Verena, Brookes, Sharon, McHugh, Domhnall, Pombo, Joaquim, Porreca, Rosa María, Dharmalingam, Gopuraja, Vernia, Santiago, Zuber, Johannes, Vannier, Jean-Baptiste, García-Escudero, Ramón, Gil, Jesús
Format: Article
Language:English
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Research Paper
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Summary:Senescence is a key barrier to neoplastic transformation. To identify senescence regulators relevant to cancer, we screened a genome-wide shRNA library. Here, we describe exportin 7 (XPO7) as a novel regulator of senescence and validate its function in telomere-induced, replicative, and oncogene-induced senescence (OIS). XPO7 is a bidirectional transporter that regulates the nuclear-cytoplasmic shuttling of a broad range of substrates. Depletion of XPO7 results in reduced levels of TCF3 and an impaired induction of the cyclin-dependent kinase inhibitor p21CIP1 during OIS. Deletion of XPO7 correlates with poorer overall survival in several cancer types. Moreover, depletion of XPO7 alleviated OIS and increased tumor formation in a mouse model of liver cancer. Our results suggest that XPO7 is a novel tumor suppressor that regulates p21CIP1 expression to control senescence and tumorigenesis.
ISSN:0890-9369
1549-5477
DOI:10.1101/gad.343269.120