Hedgehog-producing cancer cells respond to and require autocrine hedgehog activity

Samer Singh, Zhiqiang Wang, Dennis Liang Fei, Kendall E. Black, John A. Goetz, Robert Tokhunts, Camilla Giambelli, Jezabel Rodriguez-Blanco, Jun Long, Ethan Lee, Karoline J. Briegel, Pablo A. Bejarano, Ethan Dmitrovsky, Anthony J. Capobianco, David J. Robbins

Research output: Contribution to journalArticle

32 Scopus citations

Abstract

A number of Smoothened (SMO) pathway antagonists are currently undergoing clinical trials as anticancer agents. These drugs are proposed to attenuate tumor growth solely through inhibition of Hedgehog (HH), which is produced in tumor cells but acts on tumor stromal cells. The pivotal argument underlying this model is that the growth-inhibitory properties of SMO antagonists on HH-producing cancer cells are due to their off-target effects. Here, we show that the tumorigenic properties of such lung cancer cells depend on their intrinsic level of HH activity. Notably, reducing HH signaling in these tumor cells decreases HH target gene expression. Taken together, these results question the dogma that autocrine HH signaling plays no role in HH-dependent cancers, and does so without using SMO antagonists.

Original languageEnglish (US)
Pages (from-to)4454-4463
Number of pages10
JournalCancer Research
Volume71
Issue number13
DOIs
StatePublished - Jul 1 2011

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'Hedgehog-producing cancer cells respond to and require autocrine hedgehog activity'. Together they form a unique fingerprint.

  • Cite this

    Singh, S., Wang, Z., Fei, D. L., Black, K. E., Goetz, J. A., Tokhunts, R., Giambelli, C., Rodriguez-Blanco, J., Long, J., Lee, E., Briegel, K. J., Bejarano, P. A., Dmitrovsky, E., Capobianco, A. J., & Robbins, D. J. (2011). Hedgehog-producing cancer cells respond to and require autocrine hedgehog activity. Cancer Research, 71(13), 4454-4463. https://doi.org/10.1158/0008-5472.CAN-10-2313