期刊
EUROPEAN JOURNAL OF CELL BIOLOGY
卷 94, 期 5, 页码 223-233出版社
ELSEVIER GMBH
DOI: 10.1016/j.ejcb.2015.03.003
关键词
Hedgehog signaling; Transcription factor Gli; SQSTM1/p62; Autophagy; Cell proliferation
类别
资金
- Natural Science Foundation of China [31460305, 31171359, 81260021, 81200631]
- NIH [P30 CA054174]
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. (C) 2015 Elsevier GmbH. All rights reserved.
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