A Moving Target for Cancer Therapy

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Science  02 Oct 2009:
Vol. 326, Issue 5949, pp. 21
DOI: 10.1126/science.326_21b

The primary cilium, an immotile structure found on many cells, is a critical site for regulating signaling by members of the Hedgehog family of ligands. Hedgehog proteins have major roles in development, but inappropriate signaling through this pathway can contribute to certain cancers. Wong et al. and Han et al. have studied primary cilia in two cancers, human basal cell carcinomas and medulloblastomas. In keeping with earlier indications that events at the primary cilium can have both positive and negative effects on Hedgehog signaling, they found that the loss of cilia could either prevent or promote the growth of cancer cells, depending on how the Hedgehog pathway had been activated. If the cells expressed a constitutively active form of Smoothened, the upstream component that is activated when Hedgehog binds to the receptor Patched, ablation of the cilium inhibited tumor cell growth in mice. However, if the downstream transcription factor Gli2 was made constitutively active, the loss of cilia promoted tumor growth. The mechanisms at work are not precisely understood, but the authors discuss the implications for targeting therapies to inhibit Hedgehog signaling, where in some cases, the inhibition of ciliogenesis could exacerbate cancer growth rather than curb it.

Nat. Med. 15, 1055; 1062 (2009).

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