Inhibition of Hedgehog signaling pathway impedes cancer cell proliferation by promotion of autophagy

Xiaoli Tang, Libin Deng, Qi Chen, Yao Wang, Rong Xu, Chao Shi, Jia Shao, Guohui Hu, Meng Gao, Hai Rao, Shiwen Luo, Quqin Lu

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

Multiple lines of evidence implicate that aberrant activation of Hedgehog (Hh) signaling is involved in a variety of human cancers. However, the molecular mechanisms underlying how cancer cells respond to Hh inhibition remain to be elucidated. In this study, we found that blockade of Hh signaling suppresses cell proliferation in human cancer cells. Microarray analysis revealed that differentially expressed genes (DEGs) in human cancer cells are enriched in autophagy pathway in response to the inhibition of Hh signaling. Interestingly, inhibition of Hh signaling induced autophagy, whereas activation of Hh signaling by ligand treatments prevented the induction of autophagy. In addition, inhibition of autophagy by 3-methyladenine (3-MA) partially suppressed cytotoxicity induced by inhibition of Hh signaling. Finally, in autophagy deficient cells, cytotoxic effect triggered by inhibition of Hh signaling was partially reversed, indicating the modulation of autophagy by Hh signaling is autophagy-specific. These results suggest that inhibition of Hh signaling impedes cancer cell proliferation in part through induction of autophagy.

Original languageEnglish (US)
Pages (from-to)223-233
Number of pages11
JournalEuropean journal of cell biology
Volume94
Issue number5
DOIs
StatePublished - May 1 2015

Keywords

  • Autophagy
  • Cell proliferation
  • Hedgehog signaling
  • SQSTM1/p62
  • Transcription factor Gli

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Histology
  • Cell Biology

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  • Cite this

    Tang, X., Deng, L., Chen, Q., Wang, Y., Xu, R., Shi, C., Shao, J., Hu, G., Gao, M., Rao, H., Luo, S., & Lu, Q. (2015). Inhibition of Hedgehog signaling pathway impedes cancer cell proliferation by promotion of autophagy. European journal of cell biology, 94(5), 223-233. https://doi.org/10.1016/j.ejcb.2015.03.003