Limits...
The LKB1 tumor suppressor controls spindle orientation and localization of activated AMPK in mitotic epithelial cells.

Wei C, Bhattaram VK, Igwe JC, Fleming E, Tirnauer JS - PLoS ONE (2012)

Bottom Line: Orientation of mitotic spindles plays an integral role in determining the relative positions of daughter cells in a tissue.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America.

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.

Show MeSH

Related in: MedlinePlus

ZO-1 and E-cadherin localization are unaffected by LKB1 RNAi in MDCK cell cysts.Representative images of ZO-1 (red) and E-cadherin (green) immunofluorescence in control MDCK cell cysts and in cysts with LKB1 RNAi are shown. Sections were taken through the midpoint of the cyst to show the hollow lumen as well as the apical and lateral surfaces of cells at the widest part of the cyst structure. Bars, 10 µm.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3399794&req=5

pone-0041118-g003: ZO-1 and E-cadherin localization are unaffected by LKB1 RNAi in MDCK cell cysts.Representative images of ZO-1 (red) and E-cadherin (green) immunofluorescence in control MDCK cell cysts and in cysts with LKB1 RNAi are shown. Sections were taken through the midpoint of the cyst to show the hollow lumen as well as the apical and lateral surfaces of cells at the widest part of the cyst structure. Bars, 10 µm.

Mentions: To further investigate the mechanism by which LKB1 controls spindle orientation, we assayed for changes in cell polarity markers. In tumors from STK11 mutant mice, cortical actin, ZO-1, and β-catenin localization appeared normal (Figure 1 and data not shown). Analysis of control and LKB1 RNAi cysts likewise showed that the localization and appearance of cortical actin, as well as the tight junction component ZO-1 and the adherens junction mediator E-cadherin were unaffected by LKB1 reduction. This included the formation of an actin brush border at the cells’ apical/luminal surface, localization of ZO-1 at apical borders and apical cell-cell boundaries, and localization E-cadherin along lateral cell surfaces (Figures 2 and 3). Thus, LKB1 control of spindle orientation appears to be mediated through factors that function downstream of cell-cell junctions and the associated cell polarity machinery rather than by controlling cell-cell junction formation or actin cortex organization.


The LKB1 tumor suppressor controls spindle orientation and localization of activated AMPK in mitotic epithelial cells.

Wei C, Bhattaram VK, Igwe JC, Fleming E, Tirnauer JS - PLoS ONE (2012)

ZO-1 and E-cadherin localization are unaffected by LKB1 RNAi in MDCK cell cysts.Representative images of ZO-1 (red) and E-cadherin (green) immunofluorescence in control MDCK cell cysts and in cysts with LKB1 RNAi are shown. Sections were taken through the midpoint of the cyst to show the hollow lumen as well as the apical and lateral surfaces of cells at the widest part of the cyst structure. Bars, 10 µm.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3399794&req=5

pone-0041118-g003: ZO-1 and E-cadherin localization are unaffected by LKB1 RNAi in MDCK cell cysts.Representative images of ZO-1 (red) and E-cadherin (green) immunofluorescence in control MDCK cell cysts and in cysts with LKB1 RNAi are shown. Sections were taken through the midpoint of the cyst to show the hollow lumen as well as the apical and lateral surfaces of cells at the widest part of the cyst structure. Bars, 10 µm.
Mentions: To further investigate the mechanism by which LKB1 controls spindle orientation, we assayed for changes in cell polarity markers. In tumors from STK11 mutant mice, cortical actin, ZO-1, and β-catenin localization appeared normal (Figure 1 and data not shown). Analysis of control and LKB1 RNAi cysts likewise showed that the localization and appearance of cortical actin, as well as the tight junction component ZO-1 and the adherens junction mediator E-cadherin were unaffected by LKB1 reduction. This included the formation of an actin brush border at the cells’ apical/luminal surface, localization of ZO-1 at apical borders and apical cell-cell boundaries, and localization E-cadherin along lateral cell surfaces (Figures 2 and 3). Thus, LKB1 control of spindle orientation appears to be mediated through factors that function downstream of cell-cell junctions and the associated cell polarity machinery rather than by controlling cell-cell junction formation or actin cortex organization.

Bottom Line: Orientation of mitotic spindles plays an integral role in determining the relative positions of daughter cells in a tissue.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America.

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.

Show MeSH
Related in: MedlinePlus