β1 integrin expression by podocytes is required to maintain glomerular structural integrity

We previously showed that matrix metalloproteinase (MMP)-9 inhibition using an adenovirus-mediated delivery of MMP-9 small interfering RNA (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 terminal deoxynucleotidyltransferase-mediated nick end labeling staining. Ad-MMP-9 infection induced the release of cytochrome c, activation of caspase-9 and -3, and cleavage of poly(ADP-ribose) polymerase. Ad-MMP-9 infection stimulated ERK, and electrophoretic mobility shift assay indicated an increase in NF-κB activation. ERK inhibition, using a 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 the 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.

Download Full-text

The impact of quercetin on wound healing relates to changes in αV and β1 integrin expression

Experimental Biology and Medicine ◽

10.1177/1535370217712961 ◽

2017 ◽

Vol 242 (14) ◽

pp. 1424-1431 ◽

Cited By ~ 17

Author(s):

Karen M Doersch ◽

M Karen Newell-Rogers

Keyword(s):

Wound Healing ◽

Β1 Integrin ◽

Integrin Expression ◽

The Impact

Download Full-text

Cdc42 promotes transendothelial migration of cancer cells through β1 integrin

The Journal of Cell Biology ◽

10.1083/jcb.201205169 ◽

2012 ◽

Vol 199 (4) ◽

pp. 653-668 ◽

Cited By ~ 95

Author(s):

Nicolas Reymond ◽

Jae Hong Im ◽

Ritu Garg ◽

Francisco M. Vega ◽

Barbara Borda d’Agua ◽

...

Keyword(s):

Endothelial Cells ◽

Cancer Cells ◽

Cancer Cell ◽

Serum Response Factor ◽

Lung Metastases ◽

Transendothelial Migration ◽

Transcriptional Level ◽

Β1 Integrin ◽

Integrin Expression

Cancer cells interact with endothelial cells during the process of metastatic spreading. Here, we use a small interfering RNA screen targeting Rho GTPases in cancer cells to identify Cdc42 as a critical regulator of cancer cell–endothelial cell interactions and transendothelial migration. We find that Cdc42 regulates β1 integrin expression at the transcriptional level via the transcription factor serum response factor (SRF). β1 integrin is the main target for Cdc42-mediating interaction of cancer cells with endothelial cells and the underlying extracellular matrix, as exogenous β1 integrin expression was sufficient to rescue the Cdc42-silencing phenotype. We show that Cdc42 was required in vivo for cancer cell spreading and protrusion extension along blood vessels and retention in the lungs. Interestingly, transient Cdc42 depletion was sufficient to decrease experimental lung metastases, which suggests that its role in endothelial attachment is important for metastasis. By identifying β1 integrin as a transcriptional target of Cdc42, our results provide new insight into Cdc42 function.

Download Full-text