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

  • Authors:
    • Yeoun-Hee Kim
    • Jae-Chang Jung
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  • Published online on: August 23, 2012     https://doi.org/10.3892/or.2012.1986
  • Pages: 1869-1874
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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 metallo­proteinase (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.
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November 2012
Volume 28 Issue 5

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Kim Y and Jung J: 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. Oncol Rep 28: 1869-1874, 2012.
APA
Kim, Y., & Jung, J. (2012). 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. Oncology Reports, 28, 1869-1874. https://doi.org/10.3892/or.2012.1986
MLA
Kim, Y., Jung, J."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". Oncology Reports 28.5 (2012): 1869-1874.
Chicago
Kim, Y., Jung, J."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". Oncology Reports 28, no. 5 (2012): 1869-1874. https://doi.org/10.3892/or.2012.1986