Please use this identifier to cite or link to this item: http://hdl.handle.net/10400.7/867
Title: Centrosome amplification arises before neoplasia and increases upon p53 loss in tumorigenesis
Author: Lopes, Carla A.M.
Mesquita, Marta
Cunha, Ana Isabel
Cardoso, Joana
Carapeta, Sara
Laranjeira, Cátia
Pinto, António E.
Pereira-Leal, José B.
Dias-Pereira, António
Bettencourt-Dias, Mónica
Chaves, Paula
Keywords: Cancer
human cancer
Organelles
Centrosome amplification
p53
Issue Date: May-2018
Publisher: Rockefeller University Press
Citation: Carla A.M. Lopes, Marta Mesquita, Ana Isabel Cunha, Joana Cardoso, Sara Carapeta, Cátia Laranjeira, António E. Pinto, José B. Pereira-Leal, António Dias-Pereira, Mónica Bettencourt-Dias, Paula Chaves (2018). Centrosome amplification arises before neoplasia and increases upon p53 loss in tumorigenesis.J Cell Biol May 2018, jcb.201711191; DOI: 10.1083/jcb.201711191
Abstract: Centrosome abnormalities are a typical hallmark of human cancers. However, the origin and dynamics of such abnormalities in human cancer are not known. In this study, we examined centrosomes in Barrett's esophagus tumorigenesis, a well-characterized multistep pathway of progression, from the premalignant condition to the metastatic disease. This human cancer model allows the study of sequential steps of progression within the same patient and has representative cell lines from all stages of disease. Remarkably, centrosome amplification was detected as early as the premalignant condition and was significantly expanded in dysplasia. It was then present throughout malignant transformation both in adenocarcinoma and metastasis. The early expansion of centrosome amplification correlated with and was dependent on loss of function of the tumor suppressor p53 both through loss of wild-type expression and hotspot mutations. Our work shows that centrosome amplification in human tumorigenesis can occur before transformation, being repressed by p53. These findings suggest centrosome amplification in humans can contribute to tumor initiation and progression.
Description: The uploaded article version is the Epub Ahead of Print version of the article, posted online 8 May 2018. It has been submitted to peer-review.
The deposited article version contains attached the supplementary materials within the pdf.
Peer review: yes
URI: http://hdl.handle.net/10400.7/867
DOI: 10.1083/jcb.201711191
Publisher Version: http://jcb.rupress.org/content/early/2018/05/07/jcb.201711191.long
Appears in Collections:CCR - Artigos

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