Novel approach to overcome malignant cancer by targeting Y-box binding protein-1(YB-1)

2013 Fiscal Year Final Research Report

• Project/Area Number: 24650646
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Single-year Grants
• Research Field: Clinical oncology
• Research Institution: Kyushu University
• Principal Investigator: KUWANO Michihiko 九州大学, 薬学研究科(研究院), 特任教授 (80037431)
• Co-Investigator(Kenkyū-buntansha): ODA Yoshinao (70291515)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Keywords: YB-1核内局在 / 予後不良因子 / HER2発現 / ERα発現 / 乳癌 / 胃癌 / YB-1標的治療 / 分子標的薬感受性

Research Abstract

HER2 overexpression is a predictive factor of poor prognosis in patients with gastric cancer. Currently, the HER2-targeted antibody, trastuzumab, has improved the efficacy of therapy for HER2-positive advanced stomach cancer. This study demonstrated that Y-box binding protein-1 (YB-1) knockdown suppressed the expression of HER2, affecting drug resistance to lapatinib, a dual kinase inhibitor of EGFR and HER2, in gastric cancer cells. Moreover, nuclear YB-1 expression was also specifically correlated with expression of HER2 in human gastric cancer. YB-1-HER2 axis could thus contribute to further development of personalized therapeutics by HER2-targeted drugs against gastric cancer.

Research Products

• [Journal Article] Nuclear Y-box-binding protein is a poor prognostic marker and related to epidermal growth factor receptor in uterine cervical cancer (2014)
  • Author(s): Nishio, S., Ushijima, K., Yamaguchi, T., Sasajima, Y., Tsuda, H., Kasamatsu, T., Kage, M., Ono, M., Kuwano, M., and Kamura, T.
  • Journal Title: Gynecologic Oncology Volume: 132 Pages: 703-708
  • DOI: 1010.1016/j.ygyno.2014.01.045
• [Journal Article] FGFR1 activation is an escape mechanism in human lung cancer cells resistant to afatinib, a pen-EGFR family kinase inhibitor (2014)
  • Author(s): Azuma,K., Kawahara, A., Sonoda, K., Nakashima, K., Tashiro, K., Watari, K., Izumi, H., Kage, M., Kuwano, M., Ono, M., and Hoshino, T.
  • Journal Title: Oncotarget Volume: (in press)
• [Journal Article] Circadian regulation of mTOR by the ubiquitin pathway in renal cell carcinoma (2014)
  • Author(s): Okazaki, H., Matsunaga, N., Fujioka, T., Okazaki, F., Akagawa, Y., Tsurudome, Y., Ono, M,. Kuwano, M., Koyanagi, S., and Ohdo, S.
  • Journal Title: Cancer Res. Volume: 74 Pages: 543-551
  • DOI: 1010.1158/0008-5472.CAN-12-3241
• [Journal Article] Mutual regulation between Raf/MEK/ERK signaling and Y-box-binding protein-1 promotes prostate cancer progression (2013)
  • Author(s): Imada, K, Shiota, M., Kohashi, K., Kuroiwa, K., Song, Y., Sugimoto, M., Naito, S., Oda, Y.
  • Journal Title: Clin. Cancer Res. Pages: 4638-4650
  • DOI: 1010.1158/1078-0432.CCR-12-3705
• [Journal Article] Peroxiredoxins, thioredoxin, and Y-box-binding protein-1 are involved in the pathogenesis and progression of dialysis-associated renal cell carcinoma (2013)
  • Author(s): Fushimi, F., Taguchi, K., Izumi, H., Kohno, K., Kuwano, M., Ono, M., Nakashima, Y., Takesue, T., Naito, S.,and Oda, Y.
  • Journal Title: Virchows Arch Volume: 463 Pages: 553-562
  • DOI: 1010.1007/s00428-013-1460-y
• [Journal Article] Erlotinib resistance in lung cancer cells mediated by integrinβ1/Src/Akt-driven bypass signaling (2013)
  • Author(s): Kanda, R., Kawahara, A., Watari, K., Murakami, Y., Sonoda, K., Maeda, M., Fujita, H., Kage, M., Uramoto, H., Costa, C., Kuwano, M., and Ono, M.
  • Journal Title: Cancer Res. Volume: 73 Pages: 6243-6253
  • DOI: 1010.1158/0008-5472.CAN-12-4502
• [Journal Article] N-myc downstream-regulated gene 1 promotes tumor inflammatory angiogenesis through JNK activation and autocrine loop of interleukin-1αby human gastric cancer cells (2013)
  • Author(s): Murakami, Y., Watari, K., Shibata, T., Uba, M., Ureshino, H., Kawahara, A., Abe, H., Izumi, H., Mukaida, N., Kuwano, M., and Ono, M.
  • Journal Title: J. Biol. Chem. Volume: 288 Pages: 25025-25037
  • DOI: 1010.1074/jbc.M113.472068
• [Journal Article] Y-box binding protein-1 (YB-1) contributes to both HER2/ErbB2 expression and lapatinib sensitivity in human gastric cancer cells (2013)
  • Author(s): Shibata, T., Kan, H., Murakami, Y., Ureshino, H., Watari, K., Kawahara, A., Kage, M., Hattori, S., Ono, M., Kuwano, M.
  • Journal Title: Molec. Cancer Therapeut Volume: 12 Pages: 737-746
  • DOI: 1010.1158/1535-7163.MCT-12-1125
• [Journal Article] Sorting nexin 2-mediated membrane trafficking of c-Met contributes to sensitivity of molecular targeted drugs (2013)
  • Author(s): Ogi, S., Fujita, H., Kashihara, M., Yamamoto, C., Sonoda, K., Okamoto, I., Nakagawa, K., Ohdo, S., Tanaka, Y., Kuwano, M., Ono, M.
  • Journal Title: Cancer Sci. Volume: 104 Pages: 573-583
  • DOI: 1010.1111/cas.12117
• [Journal Article] N-myc downstream regulated gene 1 (NDRG1) promotes metastasis of human scirrhous gastric cancer cells through epithelial mesenchymal transition (2012)
  • Author(s): Ureshino, H., Murakami, Y., Watari, K., Izumi, H., Kawahara, A., Kage, M., Arao, T., Nishio, K., Yanagihara, K., Kinoshita, H., Kuwano, M., Ono, M.
  • Journal Title: PLoS ONE Volume: 7 Pages: e41312
  • DOI: 1010.1371/journal.pone.0041312
• [Journal Article] Loss of activating EGFR mutant gene contributes to acquired resistance to EGFR tyrosine kinase inhibitors in lung cancer cells (2012)
  • Author(s): Tabara, K., Kanda, R., Sonoda, K., Kubo, T., Murakami, Y., Kawahara, A., Azuma, K., Abe, H., Kage, M., Yoshinaga, A., Tahira, T., Hayashi, K., Arao, T., Nishio, K., Rosell, R., Kuwano, M., Ono, M.
  • Journal Title: PLoS ONE Volume: 7 Pages: e41017
  • DOI: 1010.1371/journal.pone.0041017
• [Journal Article] NDRG1/Cap43/Drg-1 may predict tumor angiogenesis and poor outcome in patients with lung cancer (2012)
  • Author(s): Azuma, K., Kawahara, A., Hattori, S., Taira, T., Tsurutani, J., Watari, K., Shibata, T., Murakami, Y., Takamori, S., Ono, M., Izumi, H., Kage, M., Yanagawa, T., Nakagawa, K., Hoshino, T., Kuwano, M.
  • Journal Title: J. Thorac. Oncol Volume: 7 Pages: 779-789
  • DOI: 1010.1097/JTO.0b013e31824c92b4
• [Journal Article] The antitumor effect of a novel angiogenesis inhibitor (an octahydronaphthalene derivative) targeting both VEGF receptor and NF-kB pathway (2012)
  • Author(s): Watari, K., Nakamura, M., Fukunaga, Y., Furuno, A., Shibata, T., Kawahara, A., Hosoi, F., Kuwano, T., Kuwano, M., and Ono, M.
  • Journal Title: Int. J.Cancer Volume: 131 Pages: 310-321
  • DOI: 10.1002/ijc.26356
• [Presentation] Y-box binding protein-1 YB-1 negatively regulates ER<expression accompanying by enhanced HER2/ErbB2 expression in breast cancer (2014)
  • Author(s): Shibata,T., Izumi, H., Kawahara,A., Hattori, S., Fukumitsu, C., Takahashi, R., Watari, K., Murakami,Y., Kohno,K., Ito, K., Kage,M., Kuwano, M., Ono.M.
  • Organizer: AACR Annual Meeting 2014
  • Place of Presentation: San Diego, CA
  • Year and Date: 20140405-09
• [Presentation] Overcoming drug resistance to gemcitabine in pancreas cancer cells by targeting activated PI3K/mTOR pathway (2014)
  • Author(s): Murakami, Y., Shinoda,A., Watari, K., Nabeshima, H., Kawahara, A., Nagayama, D., Naito, Y., Higaki, K., Inoue,M., Kuwano, M., Ono, M.
  • Organizer: AACR Annual Meeting 2014
  • Place of Presentation: San Diego, CA
  • Year and Date: 20140405-09
• [Presentation] Y-box binding protein-1(YB-1) activation may modify the responses to endocrine and HER2-targeted therapeutics in breast cancer (2014)
  • Author(s): Kuwano,M.,Shibata, T., Kawahara,A., Hattori,S., Watari, K.,Murakami,Y., Izumi,H., Kohno,K., Kage,M., Ono,M.
  • Organizer: 第12回日本臨床腫瘍学会学術集会
  • Place of Presentation: 福岡
  • Year and Date: 2014-07-18
• [Presentation] がん薬物治療の新しい創出とがん生物学-基礎研究者の立場から- (2013)
  • Author(s): 桑野信彦
  • Organizer: 第30回日本薬学会九州支部大会
  • Place of Presentation: 佐世保市(シンポジウム)
  • Year and Date: 20131207-08
• [Presentation] Integrinβ1依存性バイパスシグナルによる肺癌のEGFR-TKI耐性獲得機序-Integrin beta1/Src/Akt-driven Bypass Signaling Pathway confers EGFR-TKI Resistance in Lung Cancer Cells (2013)
  • Author(s): 小野眞弓、神田利奈、渡公佑、園田佳保里、前田雅史、村上雄一、河原明彦、鹿毛政義、浦本秀隆、桑野信彦
  • Organizer: 第72回日本癌学会学術振興会
  • Place of Presentation: 横浜市(イングリッシュオーラルセッション)
  • Year and Date: 20131003-05
• [Presentation] Y-box結合タンパク-1(YB-1)はヒト胃癌においてHER2/ErbB2発現とラパチニブの感受性を制御する (2013)
  • Author(s): 柴田智博、菅仁史、村上雄一、渡公佑、河原明彦、鹿毛政義、和泉弘人、桑野信彦、小野眞弓
  • Organizer: 第17回日本がん分子標的治療学会学術集会
  • Place of Presentation: 京都
  • Year and Date: 20130612-14
• [Presentation] Sorting nexin 2 (SNX2) controls drug sensitivity to molecular targeted anticancer agents through membrane trafficking of c-Met protein in cancer cell (2012)
  • Author(s): Ono, M., Ogi, S., Yamamoto,C., Fujita, H., Kuwano.M.
  • Organizer: AACR Annual Meeting 2012
  • Place of Presentation: Chicago, Illinois. USA
  • Year and Date: 20120331-0404
• [Presentation] NDRG1は胃癌の血管新生をIL-1/AP-1を介して促進する―NDRG1 promotes tumor angiogenesis through interleukin-1 (IL-1)/AP-1 activation pathway in human gastric cancer cells (2012)
  • Author(s): 村上雄一、渡公佑、嬉野浩樹、河原明彦、鹿毛政義、桑野信彦、小野眞弓
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: 北海道
  • Year and Date: 2012-09-20
• [Presentation] JSMO10周年記念企画わが国における臨床腫瘍学の歩みと今後の展望～JSMOの歴史と展望～ : 2)JSMO設立後10年の歩み:学術集会 (2012)
  • Author(s): 桑野信彦
  • Organizer: 第10回日本臨床腫瘍学会
  • Place of Presentation: 大阪(パネリスト)
  • Year and Date: 2012-07-26
• [Presentation] N-myc downstream regulated gene-1(NDRG1)はがん血管新生に重要な役割をはたす―NDRG1-deficient mice exhibit suppression of tumor angiogenesis and macrophage infiltration (2012)
  • Author(s): 渡公佑、柴田智博、村上雄一、桑野信彦、小野眞弓
  • Organizer: 第21回日本がん転移学会学術集会・総会
  • Place of Presentation: 広島(ワークショップ)
  • Year and Date: 2012-07-12