What is the melanoma-specific function of novel mutant MITF?

• Project/Area Number: 24700971
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Tumor biology
• Research Institution: University of Toyama
• Principal Investigator: YOKOYAMA Satoru 富山大学, 和漢医薬学総合研究所, 助教 (90613498)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 悪性黒色腫 / がん遺伝子 / MITF

Outline of Final Research Achievements

Melanoma only diagnosed less than 10% of all form of skin cancer; however, it is responsible for the majority of skin cancer related death. In 2013, it was estimated that 76.690 new cases of melanoma will be diagnosed in Unites States, and 9.480 people will die due to this disease . When diagnosed in early stage and limited to the skin, the prognosis of melanoma is curable. When it becomes metastatic melanoma, the prognosis is very poor with a 5 years survival rate less than 20%.
By using the grant support, we determined the mechanism of drug-resistance in melanoma and of the suppression of melanoma growth by natural compounds.

Research Products

• [Journal Article] Critical contribution of MCL-1 in EMT-associated chemo-resistance in A549 non-small cell lung cancer (2015)
  • Author(s): Toge M, Yokoyama S, Kato S, Sakurai H, Senda K, Doki Y, Hayakawa Y, Yoshimura N, Saiki I
  • Journal Title: Int. J. Oncol. Volume: 46 Issue: 4 Pages: 1844-1848
  • DOI: 10.3892/ijo.2015.2861
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Role of tyrosine kinase-independent phosphorylation of EGFR with activating mutation in cisplatin-treated lung cancer cells. (2015)
  • Author(s): Refaat A., Aminullah, Zhou Y., Kawanishi M., Tomaru R., Abdelhamed S., Shin M.S., Koizumi K., Yokoyama S., Saiki I., and Sakurai H.
  • Journal Title: Biochem. Biophys. Res. Commun. Volume: 458 Issue: 4 Pages: 856-861
  • DOI: 10.1016/j.bbrc.2015.02.044
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] RAC1 inhibition as a therapeutic target for gefitinib-resistant non-small cell lung cancer (2014)
  • Author(s): Kaneto N, Yokoyama S, Hayakawa Y, Kato S, Sakurai H, Saiki I
  • Journal Title: Cancer Science Volume: 105 Issue: 7 Pages: 788-794
  • DOI: 10.1111/cas.12425
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Survivin suppression through STAT3/β-catenin is essential for resveratrol-induced melanoma apoptosis. (2014)
  • Author(s): Habibie, Yokoyama S, Abdelhamed S, Awale S, Sakurai H, Hayakawa Y, Saiki I.
  • Journal Title: Int J Oncol. Volume: 45 Pages: 895-901
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Piperine Enhances the Efficacy of TRAIL-based Therapy for Triple-negative Breast Cancer Cells. (2014)
  • Author(s): Abdelhamed S, Yokoyama S, Refaat A, Ogura K, Yagita H, Awale S, Saiki I.
  • Journal Title: Anticancer Res. Volume: 34 Pages: 1893-1899
  • Peer Reviewed
• [Journal Article] Mesenchymal-transitioned cancer cells instigate the invasion of epithelial cancer cells through secretion of WNT3 and WNT5B (2014)
  • Author(s): Kato S, Hayakawa Y, Sakurai H, Saiki I, Yokoyama S
  • Journal Title: Cancer Science Volume: 105 Issue: 3 Pages: 281-289
  • DOI: 10.1111/cas.12336
  • Peer Reviewed
• [Journal Article] p38-Mediated phosphorylation of Eps15 endocytic adaptor protein. (2014)
  • Author(s): Zhou Y., Tanaka T., Sugiyama N., Yokoyama S., Kawasaki Y., Sakuma T., Ishihama Y., Saiki I., and Sakurai H.
  • Journal Title: FEBS Letters Volume: 588 Issue: 1 Pages: 131-137
  • DOI: 10.1016/j.febslet.2013.11.020
  • Peer Reviewed
• [Journal Article] Procyanidin C1 from Cinnamomi Cortex inhibits TGF-β-induced epitheli al-to-mesenchymal transition in the A549 lung cancer cell line (2013)
  • Author(s): Kin R, Kato S, Kaneto N, Sakurai H, Hayakawa Y, Li F, Tanaka K, Saiki I, Yokoyama S
  • Journal Title: International Journal of Oncology Volume: 43 Issue: 6 Pages: 1901-1906
  • DOI: 10.3892/ijo.2013.2139
  • Peer Reviewed
• [Journal Article] Berberine enhances tumor necrosis factor-related apoptosis-inducing ligand-mediated apoptosis in breast cancer. (2013)
  • Author(s): Refaat A, Abdelhamed S, Yagita H, Inoue H, Yokoyama S, Hayakawa Y, Saiki I.
  • Journal Title: Oncol Lett. Volume: 6 Pages: 840-844
  • Peer Reviewed
• [Journal Article] A flavonoid chrysin suppresses hypoxic survival and metastatic growth of mouse breast cancer cells. (2013)
  • Author(s): Lirdprapamongkol K, Sakurai H, Abdelhamed S, Yokoyama S, Maruyama T, Athikomkulchai S, Viriyaroj A, Awale S, Yagita H, Ruchirawat S, Svasti J, Saiki I.
  • Journal Title: Oncol Rep. Volume: 30 Issue: 5 Pages: 2357-2364
  • DOI: 10.3892/or.2013.2667
  • Peer Reviewed
• [Journal Article] Inverse correlation between Thr-669 and constitutive tyrosine phosphorylation in the asymmetric epidermal growth factor receptor dimer conformation. (2013)
  • Author(s): Sato K., Shin M.S., Sakimura A., Zhou Y., Tanaka T., Kawanishi M., Kawasaki Y., Yokoyama S., Koizumi K., Saiki I., and Sakurai H.
  • Journal Title: Cancer Science Volume: 104 Issue: 10 Pages: 1315-1322
  • DOI: 10.1111/cas.12225
  • Peer Reviewed
• [Journal Article] Myosin-Va contributes to manifestation of malignant-related properties in melanoma cells. (2013)
  • Author(s): Alves CP, Moraes MH, Sousa JF, Pontes CL, Ramão A, Yokoyama S, Trindade DM, Fisher DE, Espreafico EM.
  • Journal Title: J Invest Dermatol. Volume: 33 Issue: 12 Pages: 2809-2812
  • DOI: 10.1038/jid.2013.218
  • Peer Reviewed
• [Journal Article] Chrysin overcomes TRAIL resistance of cancer cells through Mcl-1 downregulation by inhibiting STAT3 phosphorylation. (2013)
  • Author(s): Lirdprapamongkol K, Sakurai H, Abdelhamed S, Yokoyama S, Athikomkulchai S, Viriyaroj A, Awale S, Ruchirawat S, Svasti J, Saiki I.
  • Journal Title: Int J Oncol. Volume: 43 Issue: 1 Pages: 329-337
  • DOI: 10.3892/ijo.2013.1926
  • Peer Reviewed
• [Journal Article] Oncogenic BRAF regulates oxidative metabolism via PGC1α and MITF. (2013)
  • Author(s): Haq R, Shoag J, Andreu-Perez P, Yokoyama S, Edelman H, et al.
  • Journal Title: Cancer Cell Volume: 23 Issue: 3 Pages: 302-315
  • DOI: 10.1016/j.ccr.2013.02.003
  • Peer Reviewed
• [Journal Article] Haq R, Yokoyama S, Hawryluk EB, Jonsson GB, Frederick DT, et al. (2013)
  • Author(s): Haq R, Yokoyama S, Hawryluk EB, Jonsson GB, Frederick DT, et al.
  • Journal Title: Proc Natl Acad Sci U S A Volume: 110 Issue: 11 Pages: 4321-4326
  • DOI: 10.1073/pnas.1205575110
  • Peer Reviewed
• [Journal Article] Identification of plant extracts sensitizing breast cancer cells to TRAIL. (2013)
  • Author(s): Abdelhamed S, Yokoyama S, Hafiyani L, Kalauni SK, Hayakawa Y, Awale S, Saiki I.
  • Journal Title: Oncology Reports Volume: 29 Issue: 5 Pages: 1991-1998
  • DOI: 10.3892/or.2013.2293
  • Peer Reviewed
• [Journal Article] Gomisin A enhances tumor necrosis factor-α-induced G1 cell cycle arrest via signal transducer and activator of transcription 1-mediated phosphorylation of retinoblastoma protein. (2012)
  • Author(s): Waiwut P, Shin MS, Yokoyama S, Saiki I, Sakurai H.
  • Journal Title: Biol Pharm Bull Volume: 35 Pages: 1997-2003
  • NAID: 130001872260
  • Peer Reviewed
• [Journal Article] Uvaridacols E-H, Highly Oxygenated Antiausterity Agents from Uvaria dac. (2012)
  • Author(s): Awale S, Ueda JY, Athikomkulchai S, Dibwe DF, Abdelhamed S, Yokoyama S, Saiki I, Miyatake R.
  • Journal Title: J Nat Prod Volume: 75 Pages: 1999-2002
  • Peer Reviewed
• [Journal Article] Anti-austerity agents from Uvaria dac and their preferential cytotoxic activity against human pancreatic cancer cell lines in nutrient deprived condition. (2012)
  • Author(s): Awale S,Ueda J,Athikomkulchai S,Abdelhamed S,Yokoyama S,Saiki I,Miyatake R.
  • Journal Title: J Nat Prod Volume: 75 Issue: 6 Pages: 1177-1183
  • DOI: 10.1021/np300295h
  • Peer Reviewed
• [Presentation] Effect of Keishibukuryogan on genetic and diet-induced obesity models. (2014)
  • Author(s): Gao F., Yokoyama S., Fujimoto M., Shimada Y., Saiki I. and Hayakawa Y.
  • Organizer: 17th International Conference of Oriental Medicine
  • Place of Presentation: Taiwan
  • Year and Date: 2014-11-01 – 2014-11-03
• [Presentation] Secretory CTGF mediates autonomous MET-like alterations in mesenchymal-transitioned A549 cells. (2014)
  • Author(s): Kato S., Yokoyama S., Hayakawa Y. and Saiki I.
  • Organizer: The 73rd Annual Meeting of the Japanese Cancer Association.
  • Place of Presentation: 横浜
  • Year and Date: 2014-09-25 – 2014-09-27
• [Presentation] Piperine enhances the efficacy of trail-based therapy for triple-negative breast cancer cells. (2014)
  • Author(s): Abdelhamed S., Yokoyama S., Refaat A., Ogura K., Awale S. and Saiki I.
  • Organizer: The 73rd Annual Meeting of the Japanese Cancer Association.
  • Place of Presentation: 横浜
  • Year and Date: 2014-09-25 – 2014-09-27
• [Presentation] メラノーマの転移抑制を目指したSLUGに対する脱ユビキチン化酵素の探索 (2014)
  • Author(s): 岩上雄亮、横山 悟、兼頭直希、加藤真一郎、早川芳弘、済木育夫
  • Organizer: The 73rd Annual Meeting of the Japanese Cancer Association.
  • Place of Presentation: 横浜
  • Year and Date: 2014-09-25 – 2014-09-27
• [Presentation] 腎がん・肺がんの転移抑制活性を有する生薬の探索とその機序解析 (2014)
  • Author(s): 横山 悟、金 諒英、村田 純、岩下 淳、加藤真一郎、兼頭直希、櫻井宏明、李 峰、田中 謙、早川芳弘、済木育夫
  • Organizer: 日本生薬学会第61回年会
  • Place of Presentation: 福岡
  • Year and Date: 2014-09-13 – 2014-09-14
• [Presentation] 漢方シグナルパネルの構築とその応用 (2014)
  • Author(s): 江島 静、横山 悟、早川芳弘、阿部貴志、済木育夫
  • Organizer: 第31回和漢医薬学会総会
  • Place of Presentation: 千葉
  • Year and Date: 2014-08-30 – 2014-08-31
• [Presentation] Sensitization for anti-cancer drug by Saikosaponin B2 (2014)
  • Author(s): Ma H., Yokoyama S., Saiki I. and Hayakawa Y.
  • Organizer: 第31回和漢医薬学会総会
  • Place of Presentation: 千葉
  • Year and Date: 2014-08-30 – 2014-08-31
• [Presentation] Identification of novel anti-inflammatory compounds from Morus alba Linne by targeting NF-B (2014)
  • Author(s): Hardianti B., Li F., Yokoyama S., Saiki I. and Hayakawa Y.
  • Organizer: 第31回和漢医薬学会総会
  • Place of Presentation: 千葉
  • Year and Date: 2014-08-30 – 2014-08-31
• [Presentation] 細胞内シグナルからみる天然薬物 (2014)
  • Author(s): 横山 悟、江島 静、阿部貴志、済木育夫
  • Organizer: 天然薬物研究方法論アカデミー 第１７回富山シンポジウム
  • Place of Presentation: 富山
  • Year and Date: 2014-07-26 – 2014-07-27
• [Presentation] 肺がんにおけるSNAILに対する脱ユビキチン化酵素の探索 (2014)
  • Author(s): 横山 悟、兼頭直希、加藤真一郎、早川芳弘、済木育夫
  • Organizer: 第23回日本がん転移学会
  • Place of Presentation: 金沢
  • Year and Date: 2014-07-10 – 2014-07-11
• [Presentation] survivinの抑制がレスベラトロールによる悪性黒色腫のアポトーシスに必須である (2014)
  • Author(s): 横山 悟、Habibie、Abdelhamed Sherif、Awale Suresh、櫻井 宏明、早川 弘、済木育夫
  • Organizer: 文部省新学術領域研究・がん支援「化学療法基盤支援活動」 第３回シンポジウム：アカデミアからの抗がん剤創薬に向けて 天然物の有効利用
  • Place of Presentation: 沖縄
  • Year and Date: 2014-05-12
• [Presentation] Resveratrol induces apoptosis in melanoma cells via downregulation of survivin expression. (2013)
  • Author(s): Saiki I., Habibie, Abdelhamed S., Awale S., Hayakawa Y. and Yokoyama S.
  • Organizer: 8th World Congress on Advances in Oncology and 16th International Symposium on Molecular Medicine
  • Place of Presentation: Greece
• [Presentation] Identification of plant extracts sensitizing breast cancer cells to TRAIL. (2013)
  • Author(s): Abdelhamed S., Yokoyama S., Lia Hafiyani, Kalauni S.K., Hayakawa Y., Awale S. and Saiki I.
  • Organizer: 第７２回日本癌学会総会
  • Place of Presentation: 横浜
• [Presentation] Mesenchymal-transitioned cancer cells instigate surrounding cancer cells to metastasis via secretion of WNT ligands. (2013)
  • Author(s): Kato S., Yokoyama S., Hayakawa Y. and Saiki I.
  • Organizer: 第７２回日本癌学会総会
  • Place of Presentation: 横浜
• [Presentation] RAC1 inhibitor suppresses gefitinib-resistant NSCLC cell migration. (2013)
  • Author(s): Kaneto N., Kato S., Yokoyama S. and Saiki I.
  • Organizer: 第７２回日本癌学会総会
  • Place of Presentation: 横浜
• [Presentation] Resveratrol induces apoptosis in melanoma cells via downregulation of survivin expression. (2013)
  • Author(s): Habibie, Abdelhamed S., Awale S., Hayakawa Y., Saiki I. and Yokoyama S.
  • Organizer: 第７２回日本癌学会総会
  • Place of Presentation: 横浜
• [Presentation] 桂皮由来のProcyanidin C1によるTGF-依存性上皮間葉転換を抑制する機能解析 (2013)
  • Author(s): 金 諒英、加藤真一郎、兼頭直希、櫻井宏明、早川芳弘、李 峰、田中 謙、済木育夫、横山 悟
  • Organizer: 第30回和漢医薬学会総会
  • Place of Presentation: 金沢
• [Presentation] Resveratrol induces apoptosis in melanoma cells via downregulation of surviving expression. (2013)
  • Author(s): , Yokoyama S., Abdelhamed S., Awale S., Hayakawa Y. and Saiki I.
  • Organizer: Second Makassar International Symposium on Pharmaceutical Science.
  • Place of Presentation: Indonesia
• [Presentation] 不均一ながん細胞間の相互作用がEMT/METを制御する (2012)
  • Author(s): 加藤真一郎，横山悟，済木育夫
  • Organizer: 第21回日本がん転移学会学術集会
  • Place of Presentation: 広島
• [Presentation] ゲフィチニブによる肺がん転移抑制機構の解析 (2012)
  • Author(s): 兼頭直希，加藤真一郎，横山悟，済木育夫
  • Organizer: 第21回日本がん転移学会学術集会
  • Place of Presentation: 広島
• [Presentation] 上皮間葉転換を抑制する桂皮の機能解析 (2012)
  • Author(s): 金諒英，加藤真一郎，兼頭直希，櫻井宏明，早川芳弘，李峰，田中謙，横山悟，済木育夫
  • Organizer: 第29回和漢医薬学会総会
  • Place of Presentation: 東京
• [Presentation] Mesenchymal-transitioned Epithelial cancer cells instigate EMT via pancreatic WNT signals (2012)
  • Author(s): Kato S., Yokoyama S., Hayakawa Y., and Saiki I.
  • Organizer: 14th International Biennial Congress of the Metastasis Research Society
  • Place of Presentation: Brisbane, Australia
• [Presentation] Berberine-induced sensitization of metastatic breast cancer to TRAIL treatment (2012)
  • Author(s): Refaat A., Diaa S., Yagita H., Yokoyama S., Hayakawa Y. and Saiki I.
  • Organizer: 第71回日本癌学会総会
  • Place of Presentation: 札幌
• [Presentation] 間葉転換した上皮系がん細胞に付与されるパラクラインWNTシグナルはEMTの更なる助長を導く (2012)
  • Author(s): 加藤真一郎，横山悟，早川芳弘，済木育夫
  • Organizer: 第71回日本癌学会総会
  • Place of Presentation: 札幌
• [Book] 生化学 第８５巻 第６号 (2013)
  • Author(s): 横山 悟
  • Total Pages: 6
  • Publisher: 日本生化学会
• [Remarks] 和漢研 病態生化学 研究業績
  • URL: http://www.inm.u-toyama.ac.jp/pb/gyoseki/index.html
• [Remarks] 和漢研 病態生化学 研究業績
  • URL: http://www.inm.u-toyama.ac.jp/pb/gyoseki/index.html
• [Remarks] 和漢研・病態生化学 研究業績
  • URL: http://www.inm.u-toyama.ac.jp/pb/gyoseki/index.html