Analysis for acetylation status of microtubules in epithelial mesenchymal transition induced by HGF/MET stimulation

• Project/Area Number: 23590431
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Human pathology
• Research Institution: Iwate Medical University
• Principal Investigator: MASUDA Tomoyuki 岩手医科大学, 医学部, 教授 (10199698)
• Co-Investigator(Kenkyū-buntansha): 柴崎 晶彦 岩手医科大学, 医学部, 助教 (20445109) ; 前沢 千早 岩手医科大学, 医学部, 教授 (10326647)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2013: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 肝癌 / HDAC6 / アセチル化 / 微小管 / EMT / 分子病理 / 肝細胞癌 / HGF / MET / TGFβ

Research Abstract

The aim of this study was to investigate the significance of HDAC6 in the invasion and metastasis activities of hepatocellular carcinoma (HCC). And we also examined the effect on epithelial mesenchymal trsnsition induced by HGF/MET system. HDAC6 expression was greater in all of the HCC cell lines compared to the primary cultures of hepatocytes. Knockdown of HDAC6 markedly downregulated the migration and invasion activities of all HCC cell lines (P<0.05). Overexpression of HDAC6 protein to a level higher than that in the corresponding normal hepatocytes was observed in 14 (20%) of the 70 primary HCCs, and was significantly correlated with high clinical stage, number of tumors, vascular invasion and intrahepatic metastasis (P<0.05). Downregulation of HDAC6 inhibited ERK1/2 tranlocation to the nuclesu. These results suggest that overexpression of the HDAC6 protein is involved in EMT of HCC cells.

Research Products

• [Journal Article] Immunohistochemistry for histone h3 lysine 9 methyltransferase and demethylase proteins in human melanomas. (2014)
  • Author(s): Miura S, Maesawa C, Shibazaki M, Yasuhira S, Kasai S, Tsunoda K, Maeda F, Takahashi K, Akasaka T, Masuda T. Immunohistochemistry for histone h3 lysine 9 methyltransferase and demethylase proteins in human melanomas.
  • Journal Title: Am J Dermatopathol Volume: 36(3) Issue: 3 Pages: 211-216
  • DOI: 10.1097/dad.0b013e3182964e02
  • Peer Reviewed / Open Access
• [Journal Article] A disintegrin and metalloproteinase 17 (ADAM17) mediates epidermal growth factor receptor transactivation by angiotensin II on hepatic stellate cells. (2014)
  • Author(s): Oikawa H, Maesawa C, Tatemichi Y, Nishinari Y, Nishiya M, Mizugai H, Ikeda A, Oikawa K, Takikawa Y, Masuda T.
  • Journal Title: Life Sci. Volume: 97(2) Issue: 2 Pages: 137-144
  • DOI: 10.1016/j.lfs.2013.12.028
  • Peer Reviewed
• [Journal Article] A somatic mutation of the KEAP1 gene in malignant melanoma is involved in aberrant NRF2 activation and an increase in intrinsic drug resistance. (2014)
  • Author(s): Miura S, Shibazaki M, Kasai S, Yasuhira S, Watanabe A, Inoue T, Kageshita Y, Tsunoda K, Takahashi K, Akasaka T, Masuda T, Maesawa C.
  • Journal Title: J Invest Dermatol. Volume: 134(2) Issue: 2 Pages: 553-556
  • DOI: 10.1038/jid.2013.343
  • Peer Reviewed
• [Journal Article] Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) with hemophagocytosis (HPS): successful treatment using high-dose chemotherapy (BFM-NHL & ALL-90) and autologous peripheral blood stem cell transplantation (2013)
  • Author(s): Sakurai E, Satoh T, Akiko YA, Maesawa C, Tsunoda K, Endo M, Akasaka T, Masuda T
  • Journal Title: J Clin Exp Hematop Volume: 53(2) Pages: 135-40
• [Journal Article] BCL2 and BCLxL are key determinants of resistance to antitubulin chemotherapeutics in melanoma cells. (2013)
  • Author(s): Watanabe A, Yasuhira S, Inoue T, Kasai S, Shibazaki M, Takahashi K, Akasaka T, Masuda T, Maesawa C.
  • Journal Title: Exp Dermatol Volume: 22(8) Issue: 8 Pages: 518-523
  • DOI: 10.1111/exd.12185
  • Peer Reviewed
• [Journal Article] Loss of HOXD10 expression induced by upregulation of miR -10b accelerates themigration and invasion activities of ovarian cancer cells (2013)
  • Author(s): Nakayama I, Shibazaki M, Yashima-Abo A, Miura F, Sugiyama T, Masuda T, MaesawaC
  • Journal Title: Int J Oncol Volume: 43(1) Issue: 1 Pages: 63-71
  • DOI: 10.3892/ijo.2013.1935
  • Peer Reviewed
• [Journal Article] Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) with hemophagocytosis (HPS): successful treatment using high-dose chemotherapy (BFM-NHL & ALL-90) and autologous peripheral blood stem cell transplantation. (2013)
  • Author(s): Sakurai E, Satoh T, Akiko YA, Maesawa C, Tsunoda K, Endo M, Akasaka T, Masuda T.
  • Journal Title: J Clin Exp Hematop. Volume: 53(2) Pages: 135-140
  • Peer Reviewed
• [Journal Article] Overexpre ssion of histone deacetylase 6 contributes to accelerated migration and invasion activity of hepatocellular carcinoma cells. (2012)
  • Author(s): Kanno K, Kanno S, Nitta H, Uesugi N, Sugai T, Masuda T, Wakabayashi G , Maesawa C
  • Journal Title: Oncol Rep. Volume: 28(3) Issue: 3 Pages: 867-73
  • DOI: 10.3892/or.2012.1898
  • Peer Reviewed
• [Journal Article] Downregulation of cylindromatosis gene, CYLD, confers a growth advantage on malignant melanoma cells while negatively regulating their migration activity (2012)
  • Author(s): Ishikawa Y, Tsunoda K, Shibazaki M, Takahashi K, Akasaka T, Masuda T, Maesawa C.
  • Journal Title: Int J Oncol Volume: 41(1) Pages: 53-60
  • DOI: 10.3892/ijo.2012.1424
  • Peer Reviewed
• [Journal Article] Sensor and effector kinases in DNAdamage checkpoint regulate capacity for homologous recombination repair offission yeast in G2 phase. (2012)
  • Author(s): Yasuhira S, Saito T, Maesawa C, Masuda T.
  • Journal Title: DNA Repair (Amst). Volume: 11(8) Issue: 8 Pages: 666-75
  • DOI: 10.1016/j.dnarep.2012.05.006
  • Peer Reviewed
• [Journal Article] Sternoclavicular joint septic arthritis following paraspinal muscle abscess and septic lumbar spondylodiscitis with epidural abscess in a patient with diabetes: a case report. (2012)
  • Author(s): Shioya N, Ishibe Y, Kan S, Masuda T, Matsumoto N, Takahashi G, Makabe H, Yamada Y, Endo S.
  • Journal Title: BMC Emerg Med Volume: 12 Pages: 7-7
  • Peer Reviewed
• [Journal Article] Overexpression of histone deacetylase 6 contributes to accelerated migration/invasion activity of hepatocellular carcinoma cells. (2012)
  • Author(s): Kanno K
  • Journal Title: Oncol Rep Volume: in press