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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Bibliographic Details
Published in:PloS one 2012-07, Vol.7 (7), p.e41118-e41118
Main Authors: Wei, Chongjuan, Bhattaram, Varun Kumar, Igwe, John C, Fleming, Elizabeth, Tirnauer, Jennifer S
Format: Article
Language:English
Subjects:
AMP-Activated Protein Kinases - metabolism
Animals
Biology
Cadherins - metabolism
Caenorhabditis elegans
Cancer
Cell cycle
Cell division
Collagen - chemistry
Control stability
Cysts
Dogs
Drug Combinations
Epithelial cells
Epithelial Cells - cytology
Gastrointestinal system
Gastrointestinal tract
Genes, Tumor Suppressor
Hypoxia
Kinases
Laminin - chemistry
LKB1 protein
Localization
Medicine
Metabolism
Mice
Microscopy, Fluorescence - methods
Microtubules - metabolism
Misalignment
Mitosis
Musculoskeletal system
Mutation
Orientation
Physiological aspects
Polarity
Proteins
Proteoglycans - chemistry
RNA Interference
RNA-mediated interference
Rodents
Spindle Apparatus
Spindles
Stem cells
Telomerase
Tumor suppressor genes
Tumors
Zonula Occludens-1 Protein - metabolism
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Summary: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.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0041118