Activation of sonic hedgehog signaling enhances cell migration and invasion by induction of matrix metalloproteinase-2 and -9 via the phosphoinositide-3 kinase/AKT signaling pathway in glioblastoma Corrigendum in /mmr/12/5/7815

Chang,Liang; Zhao,Dan; Liu,Hui‑Bin; Wang,Qiu‑Shi; Zhang,Ping; Li,Chen‑Long; Du,Wen‑Zhong; Wang,Hong‑Jun; Liu,Xing; Zhang,Zhi‑Ren; Jiang,Chuan‑Lu

doi:10.3892/mmr.2015.4229

Activation of sonic hedgehog signaling enhances cell migration and invasion by induction of matrix metalloproteinase-2 and -9 via the phosphoinositide-3 kinase/AKT signaling pathway in glioblastoma

Corrigendum in: /mmr/12/5/7815

Authors:
- Liang Chang
- Dan Zhao
- Hui‑Bin Liu
- Qiu‑Shi Wang
- Ping Zhang
- Chen‑Long Li
- Wen‑Zhong Du
- Hong‑Jun Wang
- Xing Liu
- Zhi‑Ren Zhang
- Chuan‑Lu Jiang
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Affiliations: Department of Neurosurgery, The Second Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang 150086, P.R. China, Department of Clinical Pharmacy, The Second Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang 150086, P.R. China
Published online on: August 18, 2015 https://doi.org/10.3892/mmr.2015.4229
Pages: 6702-6710
Copyright: © Chang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Aberrant hedgehog signaling contributes to the development of various malignancies, including glioblastoma (GBM). However, the potential mechanism of hedgehog signaling in GBM migration and invasion has remained to be elucidated. The present study showed that enhanced hedgehog signaling by recombinant human sonic hedgehog N‑terminal peptide (rhSHH) promoted the adhesion, invasion and migration of GBM cells, accompanied by increases in mRNA and protein levels of matrix metalloproteinase‑2 (MMP‑2) and MMP‑9. However, inhibition of hedgehog signaling with cyclopamine suppressed the adhesion, invasion and migration of GBM cells, accompanied by decreases in mRNA and protein levels of MMP‑2 and ‑9. Furthermore, it was found that MMP‑2- and MMP‑9-neutralizing antibodies or GAM6001 reversed the inductive effects of rhSHH on cell migration and invasion. In addition, enhanced hedgehog signaling by rhSHH increased AKT phosphorylation, whereas blockade of hedgehog signaling decreased AKT phosphorylations. Further experiments showed that LY294002, an inhibitor of phosphoinositide-3 kinase (PI3K), decreased rhSHH‑induced upregulation of MMP‑2 and ‑9. Finally, the protein expression of glioblastoma-associated oncogene 1 was positively correlated with levels of phosphorylated AKT as well as protein expressions of MMP‑2 and ‑9 in GBM tissue samples. In conclusion, the present study indicated that the hedgehog pathway regulates GBM-cell migration and invasion by increasing MMP-2 and MMP-9 production via the PI3K/AKT pathway.

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