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XPO7 is a tumor suppressor regulating p21CIP1-dependent senescence

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Title: XPO7 is a tumor suppressor regulating p21CIP1-dependent senescence
Authors: Innes, A
Sun, B
Wagner, V
Brookes, S
McHugh, D
Pombo, J
Porreca, RM
Dharmalingam, G
Vernia, S
Zuber, J
Vannier, J-B
García-Escudero, R
Gil, J
Item Type: Journal Article
Abstract: 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.
Issue Date: 18-Feb-2021
Date of Acceptance: 11-Jan-2021
URI: http://hdl.handle.net/10044/1/85437
DOI: 10.1101/gad.343269.120
ISSN: 0890-9369
Publisher: Cold Spring Harbor Laboratory Press
Start Page: 379
End Page: 391
Journal / Book Title: Genes and Development
Volume: 35
Copyright Statement: © 2021 Innes et al. This article, published in Genes & Development, is available under a Creative Commons License (Attribution 4.0 International), as described at http://creativecommons.org/licenses/by/4.0/.
Sponsor/Funder: European Institute of Innovation and Technology
NIHR
Keywords: TCF3
XPO7
functional screen
p21CIP1
senescence
tumor suppressor
06 Biological Sciences
11 Medical and Health Sciences
17 Psychology and Cognitive Sciences
Developmental Biology
Publication Status: Published
Online Publication Date: 2021-02-18
Appears in Collections:Department of Immunology and Inflammation
Institute of Clinical Sciences
Faculty of Medicine



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