March 19, 2013

After a lovely Spring Break with my family, HighMag is back in action.  As an oldie, Spring Break takes on a whole new meaning than it did years ago…this pregnant lady didn’t have one single beer!

 Cancer is a series of cellular mistakes, mistakes that are too far gone to fix without the help of the medical field.  Understanding the mistakes at the most basic cellular level is key to fighting the war on cancer, and a recent paper is a fine example of this.

A great model for understanding cell polarity is the intestinal epithelial sheet of cells that provides a barrier between the inside of the intestine and the body.  The different polarized domains – apical and basal – each have a discrete set of adhesion and membrane proteins trafficked to them.  One membrane trafficking protein, Rab25, is a tumor suppressor for colon cancer in both humans and mice.  A recent paper investigates the link between Rab25 and the polarized intestinal cells involved in colon cancer.  Krishnan and colleagues found that a reduction of Rab25 levels in cultured endothelial cells resulted in increased cell invasion and a loss of certain integrins, adhesion proteins, at the plasma membrane.  Rab25 loss also affected the transcription of several genes including the transcription factor ETV4, suggesting that Rab25’s effect on cell polarity is through gene regulation.  The scanning electron images above show brush border microvilli, the fingerlike-projections seen in intestinal epithelial sheets that serve to increase absorption of nutrients from the intestine.  In Rab25-reduced cells (middle row), the brush border is sparsely-packed and disorganized when compared to control cells (top row).  Bottom row shows Rab25-reduced cells in which rabbit Rab25 was reintroduced, and the rescued brush border is more organized.

Krishnan M, Lapierre LA, Knowles BC, & Goldenring JR (2013). Rab25 regulates integrin expression in polarized colonic epithelial cells. Molecular biology of the cell, 24 (6), 818-31 PMID: 23345591