Functional examination of CD147/Basigin as a regulator of tumor cell survival.

• Project/Area Number: 25461702
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Dermatology
• Research Institution: Kagoshima University
• Principal Investigator: Kanekura Takuro 鹿児島大学, 医歯学域医学系, 教授 (70177509)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2015: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2014: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2013: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
• Keywords: CD147/Basigin / 皮膚癌 / 治療 / CD147/basigin / EGFR / 悪性黒色腫 / ERシグナル / オートファジー

Outline of Final Research Achievements

We examined the function of CD147/Basigin as a regulator of tumor cell survival using a malignant melanoma cell line that expresses high level of CD147/Basigin. CD147/Basigin had no functional relation with ER signaling and autophagy which are the main defense systems against cellular stress. We found that CD147 activates EGFR which plays an important role in the cell proliferation and showed that cell growth was inhibited by the EGFR inhibitor and CD147 silencing, and additive growth inhibition was observed when these ttreatments were combined. These results would yield a improvement of therapeutic outcome in clinical settings.

Research Products

• [Journal Article] Genetic analyses of oculocutaneous albinism types 2 and 4 with eight novel mutations. (2016)
  • Author(s): Okamura K, Araki Y, Abe Y, Shigyou A, Fujiyama T, Baba A, Kanekura T, Chinen Y, Kono M, Niizeki H, Tsubota A, Konno T, Hozumi Y, Suzuki T.
  • Journal Title: J Dermatol Sci. Volume: 81 Issue: 2 Pages: 140-2
  • DOI: 10.1016/j.jdermsci.2015.10.014
  • Peer Reviewed
• [Journal Article] CD147-targeted siRNA in A375 malignant melanoma cells induces the phosphorylation of EGFR and downregulates cdc25c and MEK phosphorylation. (2016)
  • Author(s): Hatanaka M, Higashi Y, Kawai K, Su J, Zeng W, Vhen X, Kanekura T.
  • Journal Title: Oncol Lett Volume: 未定
  • Peer Reviewed
• [Journal Article] Human T-lymphotropic virus type 1 proviral loads in patients with adult T-cell leukemia-lymphoma: comparison between cutaneous type and other subtypes. (2015)
  • Author(s): Yonekura K, Utsunomiya A, Takatsuka Y, Takeuchi S, Tokunaga M, Kubota A, Takeda K, Kanzaki T, Uchida Y, Kawai K, Kanekura T.
  • Journal Title: J Dermatol Volume: 42 Issue: 12 Pages: 1143-1148
  • DOI: 10.1111/1346-8138.13004
  • Peer Reviewed
• [Journal Article] Current skin symptoms of Yusho patients exposed to high levels of 2,3,4,7,8-pentachlorinated dibenzofuran and polychlorinated biphenyls in 1968. (2015)
  • Author(s): Mitoma C, Mine Y, Utani A, Imafuku S, Akimoto T, Kanekura T, Furue M, Uchi H.
  • Journal Title: Chemosphere Volume: 137 Pages: 45-51
  • DOI: 10.1016/j.chemosphere.2015.03.070
  • Peer Reviewed
• [Journal Article] CD147-targeting siRNA induces the phosphorylation of EGFR by down-regulation of cdc25c. (2015)
  • Author(s): Hatanaka M, Higashi Y, Kawai K, Su J, Zeng W, Vhen X, Kanekura T.
  • Journal Title: Oncol Lett Volume: -
  • Peer Reviewed
• [Journal Article] Temporal expression of wound healing-related genes in skin burn injury. (2014)
  • Author(s): Kubo H, Hayashi T, ago K, Ago M, Kanekura T, Ogata M.
  • Journal Title: Legal Med Volume: 16 Pages: 8-13
  • Peer Reviewed
• [Journal Article] Effect of anti-CCR4 monoclonal antibody (Mogamulizumab) on adult T-cell leukemia-lymphoma (ATL): Cutaneous adverse reactions may predict the prognosis. (2014)
  • Author(s): Yonekura K, Kanzaki T, Gunshin K, Kawkami N, Takatsuka Y, Nakano N, Tokunaga M, Kubota A, Takeuchi S, Kanekura T, Utsunomiya A.
  • Journal Title: J Dermatol Volume: 41 Issue: 3 Pages: 239-244
  • DOI: 10.1111/1346-8138.12419
  • Peer Reviewed
• [Journal Article] Abcb10 role in heme biosynthesis in vivo: Abcb10 knockout in mice causes anemia with protoporphyrin IX and iron accumulation. (2014)
  • Author(s): Yamamoto M, Arimura H, Fukushige T, Minami K, Nishizawa Y, Tanimoto A, Kanekura T, Nakagawa M, Akiyama S, Furukawa T
  • Journal Title: Mol Cell Biol. Volume: 6 Issue: 6 Pages: 1077-84
  • DOI: 10.1128/mcb.00865-13
  • Peer Reviewed
• [Journal Article] Forensic diagnosis of ante- and postmortem burn based on aquaporin-3 gene expression in the skin (2014)
  • Author(s): Kubo H, Hayashi T, Ago K, Ago M, Kanekura T, Ogata M
  • Journal Title: Legal Med Volume: 16 Issue: 3 Pages: 128-134
  • DOI: 10.1016/j.legalmed.2014.01.008
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] DNA hypermethylation of the forkhead box protein 3 (FOXP3) prompter in CD4+ T cells of patients with systemic sclerosis. (2014)
  • Author(s): Wang YY, Wang Q, Sun XH, Liu RZ, Shu Y, Kanekura T, Huang JH, Li YP, Wang JC, Zhao M, Lu QJ, Xiao R.
  • Journal Title: Br J Dermatol Volume: 171 Issue: 1 Pages: 39-47
  • DOI: 10.1111/bjd.12913
  • Peer Reviewed
• [Journal Article] Cleaved CD147 shed from the surface of malignant melanoma cells activates MMP-2 produced by fibroblasts. (2014)
  • Author(s): Hatanaka M, Higashi Y, Fukushige T, Baba N, Kawai K, Hashiguchi T, Su J, Zeng W, Chen X, Kanekura T.
  • Journal Title: Anticancer Res Volume: 34 Pages: 7091-7096
  • Peer Reviewed
• [Journal Article] Hypomethylation and overexpression of ITGAL (CD11a) in CD4+ T cells in sytemic sclerosis. (2014)
  • Author(s): Wang Y, Shu Y, Xiao Y, Wang Q, Kanekura T, Li YP, Wang JC, Zhao M, Lu QJ, Xiao R.
  • Journal Title: Clin Epigenetics Volume: 6 Issue: 1 Pages: 25-36
  • DOI: 10.1186/1868-7083-6-25
  • Peer Reviewed
• [Journal Article] NKG2D triggers cytotoxicity in murine epidermal γδ T cells via PI3K-dependent, Syk/ZAP70-independent signaling pathway. (2014)
  • Author(s): Ibusuki A, Kawai K, Yoshida S, Uchida Y, Nitahara-Takeuchi A, Kuroki K, Kajikawa M, Ose T, Maenaka K, Kasahara M, Kanekura T.
  • Journal Title: J Invest Dermatol Volume: 134 Issue: 2 Pages: 396-404
  • DOI: 10.1038/jid.2013.353
  • Peer Reviewed
• [Journal Article] Blastic plasmacytoid dendritic cell neoplasm in human T-cell lymphotropic virus type 1 (HTLV-1) carrier: a coincidental association? (2013)
  • Author(s): Uchida Y, Kawai K, Kubo H, Takeda K, Shimokawa M, Yoshii N, Kanekura T.
  • Journal Title: Eur J Dermatol. Volume: 23 Issue: 2 Pages: 250-251
  • DOI: 10.1684/ejd.2013.1989
  • Peer Reviewed
• [Journal Article] Loss of γδ T Cells Results in Hair Cycling Defects. (2013)
  • Author(s): Kloepper JE, Kawai K, Bertolini M, Kanekura T, Paus R.
  • Journal Title: J Invest Dermatol. Volume: 133 Issue: 6 Pages: 1666-1669
  • DOI: 10.1038/jid.2013.17
  • Peer Reviewed
• [Journal Article] The etiologic role of human papillomavirus in penile cancers: a study in Vietnam (2013)
  • Author(s): Do, H. T. Koriyama, C. Khan, N. A. Higashi, M. Kato, T. Le, N. T. Matsushita, S. Kanekura, T. Akiba, S.
  • Journal Title: Br J Cancer Volume: 108 Issue: 1 Pages: 229-233
  • DOI: 10.1038/bjc.2012.583
  • Peer Reviewed
• [Journal Article] The transcription factor Snail expressed in cutaneous squamous cell carcinoma induces epithelial-mesenchymal transition and down-regulates COX-2 (2013)
  • Author(s): Shimokawa M, Haraguchi M, Kobayashi W, Higashi Y, Matsushita S, Kawai K, Kanekura T, Ozawa M.
  • Journal Title: Biochem Biophys Res Commun Volume: 430 Issue: 3 Pages: 1078-82
  • DOI: 10.1016/j.bbrc.2012.12.035
  • Peer Reviewed
• [Journal Article] Impaired neural differentiation of induced pluripotent stem cells generated from a mouse model of Sandhoff disease. (2013)
  • Author(s): Ogawa Y, Tanaka M, Tanabe M, Suzuki T, Togawa T, Fukushige T, Kanekura T, Sakuraba H, Oishi K.
  • Journal Title: PLoS One Volume: 8 Issue: 1 Pages: e55856-e55856
  • DOI: 10.1371/journal.pone.0055856
  • Peer Reviewed
• [Journal Article] Snail modulates cell metabolism in MDCK cells. (2013)
  • Author(s): Haraguchi M
  • Journal Title: Biochem Biophys Res Commun. Volume: 432 Issue: 4 Pages: 618-625
  • DOI: 10.1016/j.bbrc.2013.02.035
  • Peer Reviewed
• [Journal Article] Aberrant histone modification in peripheral blood B cells from patients with systemic sclerosis. (2013)
  • Author(s): Wang Y, Yang Y, Luo Y, Yin Y, Wang Q, Li Y, Kanekura T, Wang J, Liang G, Zhao M,Lu Q, Xiao R.
  • Journal Title: Clin Immunol. Volume: 149 Issue: 1 Pages: 46-54
  • DOI: 10.1016/j.clim.2013.06.006
  • Peer Reviewed
• [Journal Article] Japanese black vinegar “Izumi” inhibits the proliferation of human squamous cell carcinoma cells via necroptosis. (2013)
  • Author(s): Baba N, Higashi Y, Kanekura T.
  • Journal Title: Nutr Cancer. Volume: 65 Issue: 7 Pages: 1093-1097
  • DOI: 10.1080/01635581.2013.815234
  • Peer Reviewed
• [Presentation] CD147-targeted siRNA in A375 malignant melanoma cells induces the phosphorylation of EGFR by down-regulation of MEK and cdc25C. (2015)
  • Author(s): Hatanaka M, Higashi Y, Kawai K, Su J, Zeng W, Chen X, Kanekura T.
  • Organizer: 第29回表皮細胞研究会
  • Place of Presentation: ホテルニューオータニ佐賀（佐賀県佐賀市）
  • Year and Date: 2015-11-14
• [Presentation] CD147/Basigin と癌 (2015)
  • Author(s): 金蔵拓郎
  • Organizer: 愛媛大学大学院分子病態医学セミナー
  • Place of Presentation: 愛媛大学（愛媛県東温市）
  • Year and Date: 2015-09-18
  • Invited
• [Presentation] 悪性黒色腫の浸潤・転移におけるCD147/Basiginの役割－細胞間伝達機構についての検討－
  • Author(s): 畠中美帆、東 裕子、福重智子、馬場直子、河井一浩、金蔵拓郎
  • Organizer: 第165回日本皮膚科学会鹿児島地方会・総会
  • Place of Presentation: 鹿児島大学医学部（鹿児島市）
• [Presentation] CD147/Basiginと癌
  • Author(s): 金蔵拓郎
  • Organizer: 第31回岡山研究皮膚科フォーラム
  • Place of Presentation: 岡山コンベンションセンター（岡山市）
  • Invited
• [Presentation] CD147ノックダウンとEGFR阻害剤の併用による悪性黒色腫細胞の増殖抑制機序について
  • Author(s): 畠中美帆、東 裕子、金蔵拓郎
  • Organizer: 第167回日本皮膚科学会鹿児島地方会
  • Place of Presentation: 城山観光ホテル（鹿児島市）
• [Presentation] 悪性黒色腫の浸潤・転移におけるCD147/Basiginの役割－細胞間伝達機構についての検討－
  • Author(s): 畠中美帆、東 裕子、福重智子、馬場直子、河井一浩、金蔵拓郎
  • Organizer: 第2回ケラチノサイトと免疫を勉強する会
  • Place of Presentation: ホテルモントレ半蔵門（東京）