The LKB1 Tumor Suppressor Controls Spindle Orientation and Localization of Activated AMPK in Mitotic Epithelial Cells

Orientation of mitotic spindles plays an integral role in determining the relative positions of daughter cells in a tissue. LKB1 is a tumor suppressor that controls cell polarity, metabolism, and microtubule stability. Here, we show that germline LKB1 mutation in mice impairs spindle orientation in...

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Autores principales: Wei, Chongjuan, Bhattaram, Varun Kumar, Igwe, John C., Fleming, Elizabeth, Tirnauer, Jennifer S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
Materias:
Research Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3399794/
https://www.ncbi.nlm.nih.gov/pubmed/22815934
http://dx.doi.org/10.1371/journal.pone.0041118
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author Wei, Chongjuan
Bhattaram, Varun Kumar
Igwe, John C.
Fleming, Elizabeth
Tirnauer, Jennifer S.
author_facet Wei, Chongjuan
Bhattaram, Varun Kumar
Igwe, John C.
Fleming, Elizabeth
Tirnauer, Jennifer S.
author_sort Wei, Chongjuan
collection PubMed
description Orientation of mitotic spindles plays an integral role in determining the relative positions of daughter cells in a tissue. LKB1 is a tumor suppressor that controls cell polarity, metabolism, and microtubule stability. Here, we show that germline LKB1 mutation in mice impairs spindle orientation in cells of the upper gastrointestinal tract and causes dramatic mislocalization of the LKB1 substrate AMPK in mitotic cells. RNAi of LKB1 causes spindle misorientation in three-dimensional MDCK cell cysts. Maintaining proper spindle orientation, possibly mediated by effects on the downstream kinase AMPK, could be an important tumor suppressor function of LKB1.
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spelling pubmed-33997942012-07-19 The LKB1 Tumor Suppressor Controls Spindle Orientation and Localization of Activated AMPK in Mitotic Epithelial Cells Wei, Chongjuan Bhattaram, Varun Kumar Igwe, John C. Fleming, Elizabeth Tirnauer, Jennifer S. PLoS One Research Article Orientation of mitotic spindles plays an integral role in determining the relative positions of daughter cells in a tissue. LKB1 is a tumor suppressor that controls cell polarity, metabolism, and microtubule stability. Here, we show that germline LKB1 mutation in mice impairs spindle orientation in cells of the upper gastrointestinal tract and causes dramatic mislocalization of the LKB1 substrate AMPK in mitotic cells. RNAi of LKB1 causes spindle misorientation in three-dimensional MDCK cell cysts. Maintaining proper spindle orientation, possibly mediated by effects on the downstream kinase AMPK, could be an important tumor suppressor function of LKB1. Public Library of Science 2012-07-18 /pmc/articles/PMC3399794/ /pubmed/22815934 http://dx.doi.org/10.1371/journal.pone.0041118 Text en Wei et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Wei, Chongjuan
Bhattaram, Varun Kumar
Igwe, John C.
Fleming, Elizabeth
Tirnauer, Jennifer S.
The LKB1 Tumor Suppressor Controls Spindle Orientation and Localization of Activated AMPK in Mitotic Epithelial Cells
title The LKB1 Tumor Suppressor Controls Spindle Orientation and Localization of Activated AMPK in Mitotic Epithelial Cells
title_full The LKB1 Tumor Suppressor Controls Spindle Orientation and Localization of Activated AMPK in Mitotic Epithelial Cells
title_fullStr The LKB1 Tumor Suppressor Controls Spindle Orientation and Localization of Activated AMPK in Mitotic Epithelial Cells
title_full_unstemmed The LKB1 Tumor Suppressor Controls Spindle Orientation and Localization of Activated AMPK in Mitotic Epithelial Cells
title_short The LKB1 Tumor Suppressor Controls Spindle Orientation and Localization of Activated AMPK in Mitotic Epithelial Cells
title_sort lkb1 tumor suppressor controls spindle orientation and localization of activated ampk in mitotic epithelial cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3399794/
https://www.ncbi.nlm.nih.gov/pubmed/22815934
http://dx.doi.org/10.1371/journal.pone.0041118
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