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A flip of the mitotic spindle has disastrous consequences for epithelial cells
Date:7/21/2013

ent to cause loss of epithelial identity," explains Yu-ichiro Nakajima, Ph.D., a postdoctoral fellow in the Gibson lab and the study's first author. "But people in the field have hypothesized that spindle misorientation might cause tumorigenesis or even contribute to cancer development."

Initially, the group did not observe such dire consequences: Gibson says that delaminating cells generally "fall out of the epithelium" and are killed off by apoptosis, a mechanism healthy tissues use to eradicate damaged cells. But when the team experimentally inhibited apoptosis, tumor-like growths emerged at the base of the cell layer. Cells in those growths expressed genes switched on in invasive human tumors, among them the fruit fly version of human Matrix metalloproteinase-1, an epithelial cancer biomarker.

"The findings derived from epithelial biology often lead to a better understanding of cancer development," says Nakajima. "We have found that spindle orientation has a tumor-suppressive role in proliferating epithelia. So we are looking for other spindle regulators that may represent novel tumor suppressors."

Human epithelial cells do express mammalian Scribble and Discs Large proteins, and both play key roles in maintaining epithelial cell polarity, or shapa property lost in metastatic cancer cells. Whether Scribble or Discs Large act as tumor suppressors in human cancers is under investigation.

Gibson urges caution in comparing regulation of Drosophila and human epithelia. Nonetheless he notes that normal tissues in both flies and humans protect themselves by killing off misbehaving cells via apoptosis. If that mechanism failed, as is frequently observed in human cancers, disordered cells within an epithelium could escape.

"When cells are basically imprisoned in an epithelial layer, things stay nicely organized," says Gibson. "But in this study we found that simply forcing a cell to delaminate from an epithelium i
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Contact: Gina Kirchweger
gxk@stowers.org
816-806-1036
Stowers Institute for Medical Research
Source:Eurekalert

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