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Suppression of tunicamycin-induced CD44v6 ectodomain shedding and apoptosis is correlated with temporal expression patterns of active ADAM10, MMP-9 and MMP-13 proteins in Caki-2 renal carcinoma cells.
- Source :
-
Oncology reports [Oncol Rep] 2012 Nov; Vol. 28 (5), pp. 1869-74. Date of Electronic Publication: 2012 Aug 23. - Publication Year :
- 2012
-
Abstract
- CD44v6 has been shown to coordinate the activation of anti-apoptotic molecules as well as resistance to apoptosis. Here, we investigated CD44v6 ectodomain shedding in Caki-2 human renal carcinoma cells as well as its underlying mechanisms. Exposure of cells to tunicamycin (TM)-induced apoptosis was accompanied by cleavage of caspase-3, PARP-1 and CD44v6 ectodomain. TM-induced apoptosis was also closely associated with endoplasmic reticulum (ER) stress, as shown by increased expression of GRP-78 and CHOP proteins. Furthermore, induction of matrix metallo-proteinase (MMP)-13, MMP-9 and ADAM10 expression was highly stimulated by tunicamycin in a time- and dose-dependent manner. TM-induced PARP-1 cleavage was significantly inhibited by treatment with GM6001 (a broad spectrum MMP inhibitor), MMP-9/-13 inhibitor and GI254023X (specific ADAM10 inhibitor). In addition, inhibition of all examined MMPs resulted in reversal of TM-induced apoptosis as well as increased cell viability. When considering the functional implications of MMP-9 and ADAM10, it is likely that active MMP-9 and ADAM10 help regulate the cellular levels of CD44v6 through cleavage of CD44v6 ectodomain during TM-induced apoptosis of Caki-2 cells. Collectively, these findings suggest that multiple TM-induced MMPs may cooperate to induce apoptosis.
- Subjects :
- ADAM10 Protein
Anti-Bacterial Agents pharmacology
Apoptosis
Caspase 3 metabolism
Cell Line, Tumor
Dipeptides pharmacology
Endoplasmic Reticulum Chaperone BiP
Endoplasmic Reticulum Stress
Heat-Shock Proteins metabolism
Humans
Hydroxamic Acids pharmacology
Kidney Neoplasms metabolism
Matrix Metalloproteinase Inhibitors pharmacology
Poly (ADP-Ribose) Polymerase-1
Poly(ADP-ribose) Polymerases metabolism
Transcription Factor CHOP metabolism
Tunicamycin pharmacology
ADAM Proteins metabolism
Amyloid Precursor Protein Secretases metabolism
Carcinoma, Renal Cell metabolism
Hyaluronan Receptors metabolism
Matrix Metalloproteinase 13 metabolism
Matrix Metalloproteinase 9 metabolism
Membrane Proteins metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1791-2431
- Volume :
- 28
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Oncology reports
- Publication Type :
- Academic Journal
- Accession number :
- 22923171
- Full Text :
- https://doi.org/10.3892/or.2012.1986