Wednesday, July 23, 2014

Cholesterol, Wnt signaling, and Cancer - Hosein Kouros-Mehr

A recent paper* has reported a direct biological link between cholesterol and cancer.  The Wnt pathway plays an important role in cancer formation and metastasis, particularly in colorectal cancer in which the Wnt-related gene APC is frequently mutated.  In this report, the authors find that cholesterol is enriched around the Wnt-related Frizzled and LRP5/6 receptors in cancer cells.  This suggested to the authors that perhaps cholesterol itself could activate Wnt signaling.  The authors found that cholesterol directly recruits the Wnt-related Dishevelled (Dvl) scaffold protein to the cell membrane through interaction with its PDZ domain.  Dvl then activates the canonical Wnt signaling pathway.  In this way, cholesterol may directly regulate activation of canonical Wnt signaling and may regulate balance between canonical and non-canonical signaling.  Future studies will be needed to determine effects of anti-cholesterol medicines in silencing Wnt signaling and perhaps inhibiting Wnt-driven cancers.  


* ​Sheng, R., et. al. (2014).  Cholesterol selectively activates canonical Wnt signalling over non-canonical Wnt signalling.  Nature 5 (4393)

Hosein Kouros-Mehr

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