title: The LKB1 tumor suppressor controls spindle orientation and localization of activated AMPK in mitotic epithelial cells.
abstract: 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.
authors: Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America.
authors: Chongjuan
authors: C
authors: Wei
authors: Varun Kumar
authors: VK
authors: Bhattaram
authors: John C
authors: JC
authors: Igwe
authors: Elizabeth
authors: E
authors: Fleming
authors: Jennifer S
authors: JS
authors: Tirnauer
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000818:Animals; D015820:Cadherins / Q000378:metabolism; D003094:Collagen / Q000737:chemistry; D004285:Dogs; D004338:Drug Combinations; D004847:Epithelial Cells / Q000166:cytology*; D016147:Genes, Tumor Suppressor; D007797:Laminin / Q000737:chemistry; D051379:Mice; D008856:Microscopy, Fluorescence / Q000379:methods; D008870:Microtubules / Q000378:metabolism; D008938:Mitosis; D009154:Mutation; D011509:Proteoglycans / Q000737:chemistry; D034622:RNA Interference; D008941:Spindle Apparatus; D062826:Zonula Occludens-1 Protein / Q000378:metabolism
chemical_list: D015820:Cadherins; D004338:Drug Combinations; D007797:Laminin; D011509:Proteoglycans; C569043:Tjp1 protein, mouse; D062826:Zonula Occludens-1 Protein; C059485:matrigel; D003094:Collagen; D055372:AMP-Activated Protein Kinases