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Withdrawal: Blockade of tumor growth due to matrix metalloproteinase-9 inhibition is mediated by sequential activation of β1-integrin, ERK, and NF-κB
- Source :
- The Journal of biological chemistry. 295(45)
- Publication Year :
- 2020
-
Abstract
- We previously showed that MMP-9 inhibition using an adenoviral-mediated delivery of MMP-9 siRNA (Ad-MMP-9), caused senescence in medulloblastoma cells. Regardless of whether or not, Ad-MMP-9 would induce apoptosis, the possible signaling mechanism is still obscure. In this report, we demonstrate that Ad-MMP-9 induced apoptosis in DAOY cells as determined by propidium iodide and TUNEL staining. Ad-MMP-9 infection induced the release of cytochrome-c, activation of caspases-9-3, and cleavage of PARP. Ad-MMP-9 infection stimulated ERK, and EMSA indicated an increase in NF-κB activation. ERK inhibition, using kinase dead mutant for ERK, ameliorated NF-κB activation and caspase-mediated apoptosis in Ad-MMP-9 infected cells. β1-integrin expression in Ad-MMP-9 infected cells also increased, and this increase was reversed by the reintroduction of MMP-9. We found that, addition of β1 blocking antibodies inhibited Ad-MMP-9-induced ERK activation. Taken together, our results indicate that MMP-9 inhibition induces apoptosis due to altered β1 integrin expression in medulloblastoma. In addition, ERK activation plays an active role in this process and functions upstream of NF-κB activation to initiate the apoptotic signal.
- Subjects :
- Cell Biology
Molecular Biology
Biochemistry
Article
Subjects
Details
- ISSN :
- 1083351X
- Volume :
- 295
- Issue :
- 45
- Database :
- OpenAIRE
- Journal :
- The Journal of biological chemistry
- Accession number :
- edsair.doi.dedup.....b6fef0f880f2b43a8bae6fa6123c2cdc