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

被引：14

作者：

Wei, Chongjuan ^{[1
]}

Bhattaram, Varun Kumar ^{[2
]}

Igwe, John C. ^{[2
]}

Fleming, Elizabeth ^{[2
]}

Tirnauer, Jennifer S. ^{[2
,3
]}

机构：

[1] Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA

[2] Univ Connecticut, Ctr Hlth, Ctr Mol Med, Farmington, CT USA

[3] Univ Connecticut, Ctr Hlth, Neag Comprehens Canc Ctr, Farmington, CT USA

来源：

PLOS ONE | 2012年 / 7卷 / 07期

关键词：

PEUTZ-JEGHERS-SYNDROME; PROTEIN-KINASE; DROSOPHILA LKB1; CANCER; POLARITY; GENE; DIVISION; LKB1/STK11; MUTATIONS; TIGHT;

D O I：

10.1371/journal.pone.0041118

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：10

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