Abstract
The role of transglutaminase II (TGase II) in hyaluronic acid (HA)-promoted melanoma cell motility was investigated. HA induced the expression of TGase II via the nuclear factor κB (NF-kB) in melanoma cells. HA increased the Rac1 activity and phosphorylation of focal adhesion kinase (FAK). Transfection by lipofectamine of dominant-negative Rac1, and FAK-related non-kinase (FRNK), an endogenous inhibitor of FAK, suppressed the induction of TGase II. This suggests that Rac1 and FAK mediate induction of TGase II by HA. HA-promoted melanoma cell motility was inhibited by cystamine, an inhibitor of TGase II, and overexpression of TGase II enhanced melanoma cell motility through reactive oxygen species. Taken together, HA promotes melanoma cell motility through activation of Rac1, FAK, and induction of TGase II.
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References
Ahrens T, Assmann V, Fieber C, Termeer C, Herrlich P, Hofmann M, Simon JC (2001) CD44 is the principal mediator of hyaluronic-acid-induced melanoma cell proliferation. J Invest Dermatol 116(1):93–101
Bae J, Lee YS, Jeoung D (2006) Down-regulation of transglutaminase II leads to impaired motility of cancer cells by inactivation of the protein kinase, Akt, and decrease of reactive oxygen species. Biotechnol Lett 28(15):1151–1158
Bertrand P, Girard N, Delpech B, Duval C, d’Anjou J, Dauce JP (1992) Hyaluronan (hyaluronic acid) and hyaluronectin in the extracellular matrix of human breast carcinomas: comparison between invasive and non-invasive areas. Int J Cancer 52:1–6
Bourguignon LY, Zhu H, Shao L, Chen YW (2000) CD44 interaction with tiam1 promotes Rac1 signaling and hyaluronic acid-mediated breast tumor cell migration. J Biol Chem 275(3):1829–1838
Celetti A, Testa D, Staibano S, Merolla F, Guarino V, Castellone MD, Iovine R, Mansueto G, Somma P, De Rosa G, Galli V, Melillo RM, Santoro M (2005) Overexpression of the cytokine osteopontin identifies aggressive laryngeal squamous cell carcinomas and enhances carcinoma cell proliferation and invasiveness. Clin Cancer Res 2005 11(22):8019–8027
Cook AC, Chambers AF, Turley EA, Tuck AB (2006) Osteopontin induction of hyaluronan synthase 2 expression promotes breast cancer malignancy. J Biol Chem 281(34):24381–24389
Dardik R, Inbal A (2006) Complex formation between tissue transglutaminase II (tTG), vascular endothelial growth factor receptor 2 (VEGFR-2): proposed mechanism for modulation of endothelial cell response to VEGF. Exp Cell Res 312(16):2973–2982
Gaudry CA, Verderio E, Jones RA, Smith C, Griffin M (1999) Tissue transglutaminase is an important player at the surface of human endothelial cells: evidence for its externalization and its colocalization with the beta (1) integrin. Exp Cell Res 252(1):104–113
Gomes JA, Amankwah R, Powell-Richards A, Dua HS (2004) Sodium hyaluronate (hyaluronic acid) promotes migration of human corneal epithelial cells in vitro. Br. J Ophthalmol 88(6):821–825
Haroon ZA, Hettasch JM, Lai TS, Dewhirst MW, Greenberg CS (1999) Tissue transglutaminase is expressed, active, and directly involved in rat dermal wound healing and angiogenesis. FASEB J (13):1787–1795
Hartl M, Karagiannidis AI, Bister K (2006) Cooperative cell transformation by Myc/Mil(Raf) involves induction of AP-1 and activation of genes implicated in cell motility and metastasis. Oncogene 25(29):4043–4055
Janiak A, Zemskov EA, Belkin AM (2006) Cell surface transglutaminase promotes RhoA activation via integrin clustering and suppression of the Src-p190RhoGAP signaling pathway. Mol Biol Cell 17(4):1606–1619
Joshi S, Guleria R, Pan J, DiPette D, Singh US (2006) Retinoic acid receptors and tissue-transglutaminase mediate short-term effect of retinoic acid on migration and invasion of neuroblastoma SH-SY5Y cells. Oncogene 25(2):240–247
Kaartinen MT, Murshed M, Karsenty G, McKee MD (2007) Osteopontin upregulation and polymerization by transglutaminase 2 in calcified arteries of Matrix Gla protein-deficient mice. J Histochem Cytochem 55(4):375–386
Karvinen S, Pasonen-Seppanen S, Hyttinen JM, Pienimaki JP, Torronen K, Jokela TA, Tammi MI, Tammi R (2003) Keratinocyte growth factor stimulates migration and hyaluronan synthesis in the epidermis by activation of keratinocyte hyaluronan synthases 2 and 3. J Biol Chem 278(49):49495–49504
Kim MS, Park MJ, Kim SJ, Lee CH, Yoo H, Shin SH, Song ES, Lee SH (2005a) Emodin suppresses hyaluronic acid-induced MMP-9 secretion and invasion of glioma cells. Int J Oncol 27(3):839–846
Kim MS, Park MJ, Moon EJ, Kim SJ, Lee CH, Yoo H, Shin SH, Song ES, Lee SH (2005b) Hyaluronic acid induces osteopontin via the phosphatidylinositol 3-kinase/Akt pathway to enhance the motility of human glioma cells. Cancer Res 65(3):686–691
Mohan K, Pinto D, Issekutz TB (2003) Identification of tissue transglutaminase as a novel molecule involved in human CD8+ T cell transendothelial migration. J Immunol 171(6):3179–3186
Nedvetzki S, Gonen E, Assayag N, Reich R, Williams RO, Thurmond RL, Huang JF, Neudecker BA, Wang FS, Turley EA, Naor D (2004) RHAMM, a receptor for hyaluronan-mediated motility, compensates for CD44 in inflamed CD44-knockout mice: a different interpretation of redundancy. Proc Natl Acad Sci USA 101(52):18081–18086
Quan G, Choi JY, Lee DS, Lee SC (2005) TGF-beta1 up-regulates transglutaminase two and fibronectin in dermal fibroblasts: a possible mechanism for the stabilization of tissue inflammation. Arch Dermatol Res 297(2):84–90
Ropponen K, Tammi M, Parkkinen J, Eskelinen M, Tammi R, Lipponen P, Agren U, Alhava E, Kosma VM (1998) Tumor cell-associated hyaluronan as an unfavorable prognostic factor in colorectal cancer. Cancer Res 58:342–347
Stephens P, Grenard P, Aeschlimann P, Langley M, Blain E, Errington R, Kipling D, Thomas D, Aeschlimann D (2004) Crosslinking and G-protein functions of transglutaminase 2 contribute differentially to fibroblast wound healing responses. J Cell Sci 117(15):3389–3403
Thomas L, Etoh T, Stamenkovic I, Mihm MC, Byers HR (1993) Migration of human melanoma cells on hyaluronate is related to CD44 expression. J Invest Dermatol 100(2):115–120
Udabage L, Brownlee GR, Waltham M, Blick T, Walker EC, Heldin P, Nilsson SK, Thompson EW, Brown TJ (2005) Antisense-mediated suppression of hyaluronan synthase 2 inhibits the tumorigenesis and progression of breast cancer. Cancer Res 65(14):6139–6150
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This work was supported by grant (0103026-1-2) from the Basic Research Program of the Korea Science & Engineering Foundation, a grant from Korea Research Foundation and Vascular System Research Center, a grant from Korea Research Foundation (0805011-1-1), a grant from the 21C Frontier Functional Human Genome Project (FG06-2-23) from the Ministry of Science & Technology in Korea, and a grant (A050260) from the Ministry of Health and Welfare of Korea.
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Kim, Y., Park, Y.W., Lee, YS. et al. Hyaluronic acid induces transglutaminase II to enhance cell motility; role of Rac1 and FAK in the induction of transglutaminase II. Biotechnol Lett 30, 31–39 (2008). https://doi.org/10.1007/s10529-007-9496-1
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DOI: https://doi.org/10.1007/s10529-007-9496-1