Research ArticleCell Biology

Genome-Wide RNAi Screen Reveals Disease-Associated Genes That Are Common to Hedgehog and Wnt Signaling

Science Signaling  25 Jan 2011:
Vol. 4, Issue 157, pp. ra4
DOI: 10.1126/scisignal.2001225

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Yin and Yang of Stk11

A screen to link positive regulators of the Hedgehog (Hh) pathway with human disease revealed a protein that sets the threshold of Hh and Wnt signaling, two pathways involved in embryonic development and adult tissue regeneration, as well as pathological conditions, such as cancer. The tumor suppressor Stk11 (also known as Lkb1) is a kinase that has been implicated in establishing cell polarity. Jacob et al. found that Stk11 was required for the formation of full-length primary cilia, to limit production of the Gli repressor, and thereby enhanced Hh signaling. In contrast, Stk11 restricted the availability of Disheveled, limiting Wnt signaling. Thus, the absence of Stk11 resulted in a higher threshold for Hh signaling but a lower threshold for Wnt signaling.