TY - JOUR
T1 - The LKB1 tumor suppressor controls spindle orientation and localization of activated AMPK in mitotic epithelial cells
AU - Wei, Chongjuan
AU - Bhattaram, Varun Kumar
AU - Igwe, John C.
AU - Fleming, Elizabeth
AU - Tirnauer, Jennifer S.
PY - 2012/7/18
Y1 - 2012/7/18
N2 - 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.
AB - 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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U2 - 10.1371/journal.pone.0041118
DO - 10.1371/journal.pone.0041118
M3 - Article
C2 - 22815934
AN - SCOPUS:84864009034
SN - 1932-6203
VL - 7
JO - PloS one
JF - PloS one
IS - 7
M1 - e41118
ER -