PTEN suppresses epithelial–mesenchymal transition and cancer stem cell activity by downregulating Abi1

Abstract The epithelial–mesenchymal transition (EMT) is an embryonic program frequently reactivated during cancer progression and is implicated in cancer invasion and metastasis. Cancer cells can also acquire stem cell properties to self-renew and give rise to new tumors through the EMT. Inactivatio...

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Autores principales: Yanmei Qi, Jie Liu, Joshua Chao, Mark P. Scheuerman, Saum A. Rahimi, Leonard Y. Lee, Shaohua Li
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Publicado: Nature Portfolio 2020
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Acceso en línea:https://doaj.org/article/250e7653b49d4b5ab298c891dfc9a266
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spelling oai:doaj.org-article:250e7653b49d4b5ab298c891dfc9a2662021-12-02T16:06:40ZPTEN suppresses epithelial–mesenchymal transition and cancer stem cell activity by downregulating Abi110.1038/s41598-020-69698-12045-2322https://doaj.org/article/250e7653b49d4b5ab298c891dfc9a2662020-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-69698-1https://doaj.org/toc/2045-2322Abstract The epithelial–mesenchymal transition (EMT) is an embryonic program frequently reactivated during cancer progression and is implicated in cancer invasion and metastasis. Cancer cells can also acquire stem cell properties to self-renew and give rise to new tumors through the EMT. Inactivation of the tumor suppressor PTEN has been shown to induce the EMT, but the underlying molecular mechanisms are less understood. In this study, we reconstituted PTEN-deficient breast cancer cells with wild-type and mutant PTEN, demonstrating that restoration of PTEN expression converted cancer cells with mesenchymal traits to an epithelial phenotype and inhibited cancer stem cell (CSC) activity. The protein rather than the lipid phosphatase activity of PTEN accounts for the reversal of the EMT. PTEN dephosphorylates and downregulates Abi1 in breast cancer cells. Gain- and loss-of-function analysis indicates that upregulation of Abi1 mediates PTEN loss-induced EMT and CSC activity. These results suggest that PTEN may suppress breast cancer invasion and metastasis via dephosphorylating and downregulating Abi1.Yanmei QiJie LiuJoshua ChaoMark P. ScheuermanSaum A. RahimiLeonard Y. LeeShaohua LiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-13 (2020)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Yanmei Qi
Jie Liu
Joshua Chao
Mark P. Scheuerman
Saum A. Rahimi
Leonard Y. Lee
Shaohua Li
PTEN suppresses epithelial–mesenchymal transition and cancer stem cell activity by downregulating Abi1
description Abstract The epithelial–mesenchymal transition (EMT) is an embryonic program frequently reactivated during cancer progression and is implicated in cancer invasion and metastasis. Cancer cells can also acquire stem cell properties to self-renew and give rise to new tumors through the EMT. Inactivation of the tumor suppressor PTEN has been shown to induce the EMT, but the underlying molecular mechanisms are less understood. In this study, we reconstituted PTEN-deficient breast cancer cells with wild-type and mutant PTEN, demonstrating that restoration of PTEN expression converted cancer cells with mesenchymal traits to an epithelial phenotype and inhibited cancer stem cell (CSC) activity. The protein rather than the lipid phosphatase activity of PTEN accounts for the reversal of the EMT. PTEN dephosphorylates and downregulates Abi1 in breast cancer cells. Gain- and loss-of-function analysis indicates that upregulation of Abi1 mediates PTEN loss-induced EMT and CSC activity. These results suggest that PTEN may suppress breast cancer invasion and metastasis via dephosphorylating and downregulating Abi1.
format article
author Yanmei Qi
Jie Liu
Joshua Chao
Mark P. Scheuerman
Saum A. Rahimi
Leonard Y. Lee
Shaohua Li
author_facet Yanmei Qi
Jie Liu
Joshua Chao
Mark P. Scheuerman
Saum A. Rahimi
Leonard Y. Lee
Shaohua Li
author_sort Yanmei Qi
title PTEN suppresses epithelial–mesenchymal transition and cancer stem cell activity by downregulating Abi1
title_short PTEN suppresses epithelial–mesenchymal transition and cancer stem cell activity by downregulating Abi1
title_full PTEN suppresses epithelial–mesenchymal transition and cancer stem cell activity by downregulating Abi1
title_fullStr PTEN suppresses epithelial–mesenchymal transition and cancer stem cell activity by downregulating Abi1
title_full_unstemmed PTEN suppresses epithelial–mesenchymal transition and cancer stem cell activity by downregulating Abi1
title_sort pten suppresses epithelial–mesenchymal transition and cancer stem cell activity by downregulating abi1
publisher Nature Portfolio
publishDate 2020
url https://doaj.org/article/250e7653b49d4b5ab298c891dfc9a266
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AT jieliu ptensuppressesepithelialmesenchymaltransitionandcancerstemcellactivitybydownregulatingabi1
AT joshuachao ptensuppressesepithelialmesenchymaltransitionandcancerstemcellactivitybydownregulatingabi1
AT markpscheuerman ptensuppressesepithelialmesenchymaltransitionandcancerstemcellactivitybydownregulatingabi1
AT saumarahimi ptensuppressesepithelialmesenchymaltransitionandcancerstemcellactivitybydownregulatingabi1
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