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Article

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
  • View Affiliations / Copyright

    Affiliations: Department of Biology, Kyungpook National University, Daegu 702-701, Republic of Korea
  • Pages: 1869-1874
    |
    Published online on: August 23, 2012
       https://doi.org/10.3892/or.2012.1986
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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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1 

Dolai S, Pal S, Yadav RK and Adak S: Endoplasmic reticulum stress-induced apoptosis in Leishmania through Ca2+-dependent and caspase-independent mechanism. J Biol Chem. 286:13638–13646. 2011. View Article : Google Scholar : PubMed/NCBI

2 

Elbein AD: Inhibitors of the biosynthesis and processing of N-linked oligosaccharide chains. Annu Rev Biochem. 56:497–534. 1987. View Article : Google Scholar : PubMed/NCBI

3 

Delom F, Fessart D and Chevet E: Regulation of calnexin sub-cellular localization modulates endoplasmic reticulum stress-induced apoptosis in MCF-7 cells. Apoptosis. 12:293–305. 2007. View Article : Google Scholar : PubMed/NCBI

4 

Dricu A, Carlberg M, Wang M and Larsson O: Inhibition of N-linked glycosylation using tunicamycin causes cell death in malignant cells: role of down-regulation of the insulin-like growth factor 1 receptor in induction of apoptosis. Cancer Res. 57:543–548. 1997.PubMed/NCBI

5 

Hitomi J, Katayama T, Taniguchi M, Honda A, Imaizumi K and Tohyama M: Apoptosis induced by endoplasmic reticulum stress depends on activation of caspase-3 via caspase-12. Neurosci Lett. 357:127–130. 2004. View Article : Google Scholar : PubMed/NCBI

6 

Nakagawa T, Zhu H, Morishima N, et al: Caspase-12 mediates endoplasmic-reticulum-specific apoptosis and cytotoxicity by amyloid-β. Nature. 403:98–103. 2000.PubMed/NCBI

7 

Yu Q and Stamenkovic I: Localization of matrix metalloproteinase 9 to the cell surface provides a mechanism for CD44-mediated tumor invasion. Genes Dev. 13:35–48. 1999. View Article : Google Scholar : PubMed/NCBI

8 

Arch R, Wirth K, Hofmann M, et al: Participation in normal immune responses of a metastasis-inducing splice variant of CD44. Science. 257:682–685. 1992. View Article : Google Scholar : PubMed/NCBI

9 

Desai B, Ma T, Zhu J and Chellaiah MA: Characterization of the expression of variant and standard CD44 in prostate cancer cells: identification of the possible molecular mech+anism of CD44/MMP9 complex formation on the cell surface. J Cell Biochem. 108:272–284. 2009.PubMed/NCBI

10 

Naor D, Sionov RV and Ish-Shalom D: CD44: structure, function, and association with the malignant process. Adv Cancer Res. 71:241–319. 1997. View Article : Google Scholar : PubMed/NCBI

11 

Yamane N, Tsujitani S, Makino M, Maeta M and Kaibara N: Soluble CD44 variant 6 as a prognostic indicator in patients with colorectal cancer. Oncology. 56:232–238. 1999. View Article : Google Scholar : PubMed/NCBI

12 

Wielenga VJ, Heider KH, Offerhaus GJ, et al: Expression of CD44 variant proteins in human colorectal cancer is related to tumor progression. Cancer Res. 53:4754–4756. 1993.PubMed/NCBI

13 

Jung T, Gross W and Zoller M: CD44v6 coordinates tumor matrix-triggered motility and apoptosis resistance. J Biol Chem. 286:15862–15874. 2011. View Article : Google Scholar : PubMed/NCBI

14 

Mielgo A, van Driel M, Bloem A, Landmann L and Gunthert U: A novel antiapoptotic mechanism based on interference of Fas signaling by CD44 variant isoforms. Cell Death Differ. 13:465–477. 2006. View Article : Google Scholar : PubMed/NCBI

15 

Fini ME and Girard MT: The pattern of metalloproteinase expression by corneal fibroblasts is altered by passage in cell culture. J Cell Sci. 97:373–383. 1990.PubMed/NCBI

16 

Girard MT, Matsubara M, Kublin C, Tessier MJ, Cintron C and Fini ME: Stromal fibroblasts synthesize collagenase and stromelysin during long-term tissue remodeling. J Cell Sci. 104:1001–1011. 1993.PubMed/NCBI

17 

Sternlicht MD and Werb Z: How matrix metalloproteinases regulate cell behavior. Annu Rev Cell Dev Biol. 17:463–516. 2001. View Article : Google Scholar : PubMed/NCBI

18 

Kessenbrock K, Plaks V and Werb Z: Matrix metalloproteinases: regulators of the tumor microenvironment. Cell. 141:52–67. 2010. View Article : Google Scholar : PubMed/NCBI

19 

Smith KM, Gaultier A, Cousin H, Alfandari D, White JM and DeSimone DW: The cysteine-rich domain regulates ADAM protease function in vivo. J Cell Biol. 159:893–902. 2002. View Article : Google Scholar : PubMed/NCBI

20 

Anderegg U, Eichenberg T, Parthaune T, et al: ADAM10 is the constitutive functional sheddase of CD44 in human melanoma cells. J Invest Dermatol. 129:1471–1482. 2009. View Article : Google Scholar : PubMed/NCBI

21 

Huh MI, Lee YM, Seo SK, et al: Roles of MMP/TIMP in regulating matrix swelling and cell migration during chick corneal development. J Cell Biochem. 101:1222–1237. 2007. View Article : Google Scholar : PubMed/NCBI

22 

Nagano O, Murakami D, Hartmann D, et al: Cell-matrix interaction via CD44 is independently regulated by different metalloproteinases activated in response to extracellular Ca(2+) influx and PKC activation. J Cell Biol. 165:893–902. 2004.PubMed/NCBI

23 

Pacheco-Rodriguez G, Steagall WK, Crooks DM, et al: TSC2 loss in lymphangioleiomyomatosis cells correlated with expression of CD44v6, a molecular determinant of metastasis. Cancer Res. 67:10573–10581. 2007. View Article : Google Scholar : PubMed/NCBI

24 

Dreier R, Grassel S, Fuchs S, Schaumburger J and Bruckner P: Pro-MMP-9 is a specific macrophage product and is activated by osteoarthritic chondrocytes via MMP-3 or a MT1-MMP/MMP-13 cascade. Exp Cell Res. 297:303–312. 2004. View Article : Google Scholar : PubMed/NCBI

25 

Hernandez Rios M, Sorsa T, Obregon F, et al: Proteolytic roles of matrix metalloproteinase (MMP)-13 during progression of chronic periodontitis: initial evidence for MMP-13/MMP-9 activation cascade. J Clin Periodontol. 36:1011–1017. 2009.PubMed/NCBI

26 

Lazebnik YA, Kaufmann SH, Desnoyers S, Poirier GG and Earnshaw WC: Cleavage of poly(ADP-ribose) polymerase by a proteinase with properties like ICE. Nature. 371:346–347. 1994. View Article : Google Scholar : PubMed/NCBI

27 

Ferreira KS, Kreutz C, Macnelly S, et al: Caspase-3 feeds back on caspase-8, Bid and XIAP in type I Fas signaling in primary mouse hepatocytes. Apoptosis. 17:503–515. 2012. View Article : Google Scholar : PubMed/NCBI

28 

Oyadomari S and Mori M: Roles of CHOP/GADD153 in endoplasmic reticulum stress. Cell Death Differ. 11:381–389. 2004. View Article : Google Scholar : PubMed/NCBI

29 

Ponta H, Sleeman J, Dall P, Moll J, Sherman L and Herrlich P: CD44 isoforms in metastatic cancer. Invasion Metastasis. 14:82–86. 1994.PubMed/NCBI

30 

Spessotto P, Rossi FM, Degan M, et al: Hyaluronan-CD44 interaction hampers migration of osteoclast-like cells by down-regulating MMP-9. J Cell Biol. 158:1133–1144. 2002. View Article : Google Scholar : PubMed/NCBI

31 

Samanna V, Ma T, Mak TW, Rogers M and Chellaiah MA: Actin polymerization modulates CD44 surface expression, MMP-9 activation, and osteoclast function. J Cell Physiol. 213:710–720. 2007. View Article : Google Scholar : PubMed/NCBI

32 

Seipel D, Oliveira BC, Resende TL, et al: Toxoplasma gondii infection positively modulates the macrophages migratory molecular complex by increasing matrix metalloproteinases, CD44 and alpha v beta 3 integrin. Vet Parasitol. 169:312–319. 2010. View Article : Google Scholar

33 

Chetty C, Vanamala SK, Gondi CS, Dinh DH, Gujrati M and Rao JS: MMP-9 induces CD44 cleavage and CD44 mediated cell migration in glioblastoma xenograft cells. Cell Signal. 24:549–559. 2012. View Article : Google Scholar : PubMed/NCBI

34 

Ponta H, Sherman L and Herrlich PA: CD44: from adhesion molecules to signalling regulators. Nat Rev Mol Cell Biol. 4:33–45. 2003. View Article : Google Scholar : PubMed/NCBI

35 

Morrison H, Sherman LS, Legg J, et al: The NF2 tumor suppressor gene product, merlin, mediates contact inhibition of growth through interactions with CD44. Genes Dev. 15:968–980. 2001. View Article : Google Scholar : PubMed/NCBI

36 

Wittig BM, Johansson B, Zoller M, Schwarzler C and Gunthert U: Abrogation of experimental colitis correlates with increased apoptosis in mice deficient for CD44 variant exon 7 (CD44v7). J Exp Med. 191:2053–2064. 2000. View Article : Google Scholar : PubMed/NCBI

37 

Lesley J, English N, Perschl A, Gregoroff J and Hyman R: Variant cell lines selected for alterations in the function of the hyaluronan receptor CD44 show differences in glycosylation. J Exp Med. 182:431–437. 1995. View Article : Google Scholar : PubMed/NCBI

38 

Sleeman J, Rudy W, Hofmann M, Moll J, Herrlich P and Ponta H: Regulated clustering of variant CD44 proteins increases their hyaluronate binding capacity. J Cell Biol. 135:1139–1150. 1996. View Article : Google Scholar : PubMed/NCBI

39 

Stevens JW, Palechek PL, Griebling TL, Midura RJ, Rokhlin OW and Cohen MB: Expression of CD44 isoforms in human prostate tumor cell lines. Prostate. 28:153–161. 1996. View Article : Google Scholar : PubMed/NCBI

40 

Yu Q, Toole BP and Stamenkovic I: Induction of apoptosis of metastatic mammary carcinoma cells in vivo by disruption of tumor cell surface CD44 function. J Exp Med. 186:1985–1996. 1997. View Article : Google Scholar : PubMed/NCBI

41 

Isacke CM and Yarwood H: The hyaluronan receptor, CD44. Int J Biochem Cell Biol. 34:718–721. 2002. View Article : Google Scholar : PubMed/NCBI

42 

Kobayashi T: Suppression of matrix metalloproteinase-9 expression in undifferentiated, non-apoptotic keratinocytes is abrogated by the cleavage of poly(ADP-ribose) polymerase-1. Apoptosis. 16:1205–1216. 2011. View Article : Google Scholar : PubMed/NCBI

43 

Yu Q and Stamenkovic I: Transforming growth factor-beta facilitates breast carcinoma metastasis by promoting tumor cell survival. Clin Exp Metastasis. 21:235–242. 2004. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
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
Copy and paste a formatted citation
x
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
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