Control mechanism of anti-cancer drug resistance by sphingolipid

2011 Fiscal Year Final Research Report

• Project/Area Number: 21590061
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Biological pharmacy
• Research Institution: Gifu University
• Principal Investigator: BANNO Yoshiko 岐阜大学, 大学院・医学系研究科, 非常勤講師 (50116852)
• Co-Investigator(Kenkyū-buntansha): OSAWA Yousuke 岐阜大学, 大学院・医学系研究科, 助教 (60447787) ; KYOUGASHIMA Mamoru 愛知県がんセンター(研究所), 分子病態学部, 室長 (50225091)
• Co-Investigator(Renkei-kenkyūsha): NAKAMURA Mitsuhiro 岐阜薬科大学, 臨床薬学, 准教授 (30433204) ; MURATE Takashi 名古屋大学, 保健学科, 教授 (30239537)
• Project Period (FY): 2009 – 2011
• Keywords: スフィンゴ脂質 / 抗癌剤耐性 / 大腸癌 / がん幹細胞 / アポトーシス

Research Abstract

We has shown that sphingosine kinase(SPHK) 1 activity and protein expression regulated oxaliplatin(L-OHP) sensitivity in human colon cancer cells. In L-OHP resistant human colon cancer cell lines, SPHK1, CD44, endogenous phosphorylated-Akt and phosphorylated-ERK levels were much higher than those of sensitive cells. The elevation of CD44 protein level was abolished by the inhibition of ERK phosphorylation. The exogenous stimulation with sphingosine 1-phosphate(S1P) induced increase of ERK phosphorylation and CD44 protein expression in HCT116 cells. These S1P-induced increases were also suppressed by MEK inhibitor. These findings indicate that SPHK1 and its product, S1P, contribute to the regulation of CD44 protein expression through ERK signaling pathway in human colon cancer cells.

Research Products

• [Journal Article] Cayman Ataxia-Related Protein is a Presynapse-Specific Caspase-3 Substrate (2011)
  • Author(s): Itoh, M ; Li, SM ; Ohta, K Yamada, A ; Hayakawa-Yano, Y ; Ueda, M ; Hida, Y ; Suzuki, Y ; Ohta, E ; Mizuno, A ; Banno, Y ; Nakagawa, T
  • Journal Title: NEUROCHEM. RES Volume: 36 Pages: 1304-1313
  • Peer Reviewed
• [Journal Article] Heterogeneous sphingosine-1-phosphate lyase gene expression and its regulatory mechanism in human lung cancer cell lines (2011)
  • Author(s): Ito, H., Yoshida, K. Murakami, M., Hagiwara, K., Sasaki, N., Kobayashi, M., Takagi, A., Kijima, T., Sobue, S., Suzuki, M., Tamiya-Koizumi, K., Nakamura, M., Banno, Y., Nozawa, Y., Murate, T Biochim. Biophys
  • Journal Title: Acta-Molecular and Cell Biology of Lipids Volume: 1811 Pages: 119-128
  • Peer Reviewed
• [Journal Article] Acid sphingomyelinase regulates glucose and lipid metabolism in hepatocytes through AKT activation and AMP-activated protein kinase suppression (2011)
  • Author(s): Osawa, Y., Seki, Y., Kodama, A., Suetsugu, K., Miura, M., Adachi, H., Ito, Y., Shiratori, Y., Banno, Y., Olefsky, J. M., Nagaki, M., Moriwaki, H., Brenner, D. A., Seishima, M.
  • Journal Title: FASEB J Volume: 25 Pages: 1133-1144
  • Peer Reviewed
• [Journal Article] Involvement of the aldo-keto reductase AKR1B10 in mitomycin-c resistance via ROS dependent mechanisms (2011)
  • Author(s): T. Matsunaga, Y. Yamane, K. Iida, S. Endo, O. El-Kabbani, Y. Banno, A. Hara
  • Journal Title: Anti-Cancer Drugs Volume: 22 Pages: 402-408
• [Journal Article] The pivotal role of intracellular calcium in oxaliplatin-induced inhibition of neurite outgrowth but not cell death in differentiated PC12 cells (2011)
  • Author(s): M. Takeshita, Y. Banno, M. Nakamura, H. Teramachi, T. Tsuchiya, Y. Itoh
  • Journal Title: Chem. Res. Toxicol. Volume: 24 Pages: 1845-1852
  • Peer Reviewed
• [Journal Article] Sphingosine Kinase 1/S1P Pathway Involvement in the GDNF-Induced GAP43 Transcription (2011)
  • Author(s): Murakami, M ; Ito, H ; Hagiwara, K Kobayashi, M ; Hoshikawa, A ; Takagi, A ; Kojima, T ; Tamiya-Koizumi, K ; Sobue, S ; Ichihara, M ; Suzuki, M ; Banno, Y Nozawa, Y Murate, T.
  • Journal Title: J. CELL. BIOCHEM. Volume: 112 Pages: 3449-3458
  • Peer Reviewed
• [Journal Article] G(s) and G(q) signalings regulate hPEM-2-induced cell responses in Neuro-2a cells (2011)
  • Author(s): Nagae, R Sato, K ; Yasui, Y Banno, Y Nagase, T ; Ueda, H
  • Journal Title: BIOCHEM. BIOPHYS. RES. COMMUN. Volume: 415 Pages: 168-173
  • Peer Reviewed
• [Journal Article] S1P3-mediated cardiac fibrosis in sphingosine kinase 1 transgenic mice involves reactive oxygen species (2010)
  • Author(s): Takuwa N., Ohkura S., Takashima S., Ohtani K., Okamoto Y., Tanaka T., Hirano K., Usui S., Wang F., Du W., Yoshioka K., Banno Y., Sasaki M., Ichi I., Okamura M., Sugimoto N., Mizugishi K., Nakamua Y., Ishi I., Takamura M., Kaneko S., Kojo S., Satouchi K.,
  • Journal Title: Cardiovasc. Res. Volume: 85 Pages: 484-493
  • Peer Reviewed
• [Journal Article] Mechanism of increased PLD1 gene expression During Early Adipocyte Differentiation Process of Mouse Cell Line (2010)
  • Author(s): Siqiang Gao, Masashi Murakami, Hiromi Ito, Kayo Yoshida, Yoko Tagawa, Kazumi Hagiwara, Akira Takagi, Tetsuhito Kojima, Motoshi Suzuki, Yoshiko Banno, Yoshinori Nozawa, Takashi Murate J
  • Journal Title: Cellular Biochem Volume: 109 Pages: 375-382
  • Peer Reviewed
• [Journal Article] ATRA inhibits ceramide kinase transcription in a human neuroblastoma cell line, SH-SY5Y cells : the role of COUP-TFI (2010)
  • Author(s): M. Murakami, H. Ito, K. Hagiwara, K. Yoshida, S. Sobue, M. Ichihara, A. Takagi, T. Kojima, K. Tanaka, K. Koizumi-T, M. Kyogashima, M. Suzuki, Y. Banno, Y. Nozawa, and T. Murate
  • Journal Title: J. Neurochem Volume: 112 Pages: 511-520
  • Peer Reviewed
• [Journal Article] Phospholipase D family member 4, a transmembrane glycoprotein with no phospholipase D activity, expressed in spleen and early postnatal microglia (2010)
  • Author(s): F. Yoshikawa, Y. Banno, Y. Otani, Y. Yamaguchi, Y. Nagakura-Takagi, N. Morita, Y. Sato, C. Saruta, H. Nishibe, T. Sadakata, Y. Shinoda, K. Hayashi, Y. Mishima, H. Baba, and T. Furuichi
  • Journal Title: PLOS ONE Volume: 5(11) Pages: 1-13
  • Peer Reviewed
• [Journal Article] Sphingosine kinase isoforms regulate oxaliplatin sensitivity of human colon cancer cells through ceramide accumulation and Akt activation (2009)
  • Author(s): Nemoto, S., Nakamura, M., Osawa, Y., Kono, K., Itoh, Y., Okano, Y., Murate, T., Hara, A., Ueda, H., Nozawa, Y., Banno, Y.
  • Journal Title: J. Biol. Chem. Volume: 284 Pages: 10422-10432
  • Peer Reviewed
• [Journal Article] Transcriptional regulation of neutral sphingomyelinase 2 gene expression of a human breast cancer cell line, MCF-7, induced by the anti-cancer drug, daunorubicin (2009)
  • Author(s): Hiromi Ito, Masashi Murakami, Ayako Furuhata, Siqiang Gao, Kayo Yoshida, Sayaka Sobue, Kazumi Hagiwara, Akira Takagi, Tetsuhito Kojima, Motoshi Suzuki, Yoshiko Banno, Koji Tanaka ; Keiko Tamiya-Koizumi, Yoshinori Nozawa, Takashi Murate
  • Journal Title: Biochim. Biophys. Acta Volume: 1789 Pages: 675-762
  • Peer Reviewed
• [Journal Article] Mechanism of increased PLD1 gene expression during early adipocyte differentiation process of mouse cell line 3T3-L1 (2009)
  • Author(s): Gao, S., Murakami, M., Ito, H., Yoshida, K., Tagawa, Y., Hagiwara, K., Takagi, A., Kojima, T., Suzuki, M., Banno, Y., Nozawa, Y. and Murate, T.
  • Journal Title: Nagoya J. Med. Sci. Volume: 71 Pages: 127-136
  • Peer Reviewed
• [Presentation] The effect on acid sphingomyelinase(ASMase) by resveratrol (2011)
  • Author(s): 伊藤裕美、萩原和美、田中広治、小林美沙、星川あすか、水谷直貴、高木明、小嶋哲人、小泉恵子、中村光浩、坂野喜子、野澤義則、村手隆
  • Organizer: 第84回日本生化学会大会
  • Place of Presentation: 京都
  • Year and Date: 20110921-24
• [Presentation] オキザリプラチン耐性大腸癌細胞におけるアルドケト還元酵素1B10発現と増殖能の関連性 (2011)
  • Author(s): 和田康弘、松永俊之、飯田佳子、友国宅充、北條杏季、遠藤智史、坂野喜子、原明
  • Organizer: 第84回日本生化学会大会
  • Place of Presentation: 京都
  • Year and Date: 20110921-24
• [Presentation] Sphingosine kinase regulates oxaliplatin sensitivity of human colon cancer cells through ceramide accumulation and CD44 expression (2011)
  • Author(s): S. Kawahara, M. Nakamura, T. Murate, A. Hara, Y. Nozawa, Y. Banno
  • Organizer: 51th International Conference on the Bioscience of Lipids
  • Place of Presentation: Bilbao
  • Year and Date: 20110907-11
• [Presentation] Sphingosine kinase 1 and its product, sphingosine 1-phosphate are involved in glial cell-line derived neurotrophic factor-induced GAP-43 gene regulation (2010)
  • Author(s): Murakami, M., Ito, H., Hagiwara, K., Sasaki, N., Kobayashi, M., Hoshikawa, A., Takagi, A., Kojima, T., T-Koizumi, K., Banno, Y., Nozawa, Y., Murate, T.
  • Organizer: 第83回日本生化学大会、第33回日本分子生物学会年会合同大会
  • Place of Presentation: 神戸
  • Year and Date: 20101207-10
• [Presentation] The regulatory mechanism of neutral shingomyelinase 2 gene expression induced by all trans retinoic acid(ATRA) in MCF7 cells (2010)
  • Author(s): Ito, H., Murakami, M., Hagiwara, K., Sasaki, N., Kobayashi, S., Hoshikawa, A., Takagi, A., Kojima, T., Banno, Y., Koizumi, K., Nakamura M., Nozawa, Y., Murate, T.
  • Organizer: 第83回日本生化学大会、第33回日本分子生物学会年会合同大会
  • Place of Presentation: 神戸
  • Year and Date: 20101207-10
• [Presentation] スプィンゴ脂質代謝による抗癌剤感受性とCD44発現の調節機構 (2010)
  • Author(s): 川原さと実、中村光浩、大辻陽子、原明、村手隆、野澤義則、坂野喜子
  • Organizer: 第83回日本生化学大会、第33回日本分子生物学会年会合同大会
  • Place of Presentation: 神戸
  • Year and Date: 20101207-10
• [Presentation] シスプラチンによる神経細胞様PC12細胞の突起退縮に対するデセン酸の作用 (2010)
  • Author(s): 大塚万祐子、中村光浩、川原さと実、竹下未希、原明、坂野喜子、土屋照雄
  • Organizer: 第83回日本生化学大会、第33回日本分子生物学会年会合同大会
  • Place of Presentation: 神戸
  • Year and Date: 20101207-10
• [Presentation] Down regulation of neutral ceramidase induces neural differentiation in human neuroblastoma SH-SY5Y cells (2010)
  • Author(s): Tanak, K., Tamiya-Koizumi, K., Hagiwara, K., Murakami, M., Murate, T., Banno, Y., Nakamura, M., Kannagi, R., Kyougashima, M.
  • Organizer: 第83回日本生化学大会、第33回日本分子生物学会年会合同大会
  • Place of Presentation: 神戸
  • Year and Date: 20101207-10
• [Presentation] Hybrid liposome induced alteration of lipid constituent in cancer cell membrane (2010)
  • Author(s): K. Cao, K. Tamiya-Koizumi, K. Tanaka, M. Kyogashima, M. Nakamura, Y. Banno, Y. Komizua, R. Ueoka and M. Suzuki
  • Organizer: The 4th International Synposium on "Molecular Science of Fluctuations toward Biological Functions"
  • Year and Date: 20101020-23
• [Presentation] The regulatory mechanism of NSMase2 gene expression by ATRA in MCF7 cells (2010)
  • Author(s): H. Ito, M. Murakami, K. Hagiwara, N. Sakai, M. Kobayashi, A. Hoshikawa, A. Takagi, T. Kojima, Y. Banno, K. Tamiya-Koizumi, M. Nakamura, Y. Nozawa, T. Murate
  • Organizer: 51th International Conference on the Bioscience of Lipids
  • Place of Presentation: Bilbao
  • Year and Date: 20100907-11
• [Presentation] Heterogeneous sphingpsine-1-phosphate lyase gene expression and its regulatory mechanism in human lung cancer cell lines (2010)
  • Author(s): T. Murate, K. Yoshida, H. Ito, M. Murakami, K. Hagiware, N. Sakai, A. Takagi, T. Kojima, S. Sobue, M. Suzuki, K. Tamiya-Koizumi, M. Nakamura, Y. Banno, Y. Nozawa
  • Organizer: 51th International Conference on the Bioscience of Lipids
  • Place of Presentation: Bilbao
  • Year and Date: 20100907-11
• [Presentation] 各種ヒト肺がん細胞株におけるスフィンゴシン1リン酸リアーゼの発現レベルとその調節機序 (2010)
  • Author(s): 村手隆、吉田佳世、伊藤裕美、村上真史、佐々木法子、小林美沙、星川あすか、高木明、小嶋哲人、小泉恵子、中村光浩、坂野喜子、野澤義則
  • Organizer: 第5回スフィンゴテラピー研究会
  • Place of Presentation: 米子
  • Year and Date: 20100716-17
• [Presentation] スフィンゴ脂質代謝による抗癌剤耐性の制御機構解明:がん幹細胞との関連性 (2010)
  • Author(s): 川原さと実、中村光浩、大塚万祐子、原明、村手隆、野澤義則、坂野喜子
  • Organizer: 第5回スフィンゴテラピー研究会
  • Place of Presentation: 米子
  • Year and Date: 20100716-17
• [Presentation] スフィンゴシンキナーゼによる抗癌剤感受性の制御機構. Regulation of anticancer drug sensitivity by sphingosine kinase in colon cancer cells (2009)
  • Author(s): 川原さと実、河野早紀、竹下未希、中村光浩、岡野幸雄、原明、伊藤善規、土屋照雄、村手隆、野澤義則、坂野喜子
  • Organizer: 第82回日本生化学大会
  • Place of Presentation: 神戸
  • Year and Date: 20091021-24
• [Presentation] ヒト乳癌細胞株MCF7細胞におけるATRAによるNSMase2の発現調節 (2009)
  • Author(s): 伊藤裕美、村上真史、萩原和美、吉田佳世、田川容子、佐々木法子、祖父江沙矢加、高木明、小嶋哲1、坂野喜子、田中公司、京ケ島守、小泉恵子、野澤義則、村手隆
  • Organizer: 第82回日本生化学大会
  • Place of Presentation: 神戸
  • Year and Date: 20091021-24
• [Presentation] 各種肺癌細胞株におけるSphingosine-1-phosphate lyase(SPL)転写調節機序の解析 (2009)
  • Author(s): 吉田佳世、村上真史、伊藤裕美、田川容子、佐々木法子、高木明、小嶋哲人、坂野喜子、野澤義則、村手隆
  • Organizer: 第82回日本生化学大会
  • Place of Presentation: 神戸
  • Year and Date: 20091021-24
• [Presentation] Daunorubisin-induced neutral sphingo-myelinase 2 gene expression in MCF7 cells (2009)
  • Author(s): H. Ito, M. Murakami, K. Hagiwara, K. Yoshida1, Y. Tagawa1, N. Sasaki, A. Takagi, T. Kojima, Y. Banno, K. Tamiya-Koizumi, Y. Nozawa, T. Murate
  • Organizer: 50th International Conference on the Bioscience of Lipids
  • Place of Presentation: Regensburg, Germany
  • Year and Date: 20090901-05
• [Presentation] Regulatory mechanism of ATRA-induced ceramide kinase gene suppression in a human neuroblastoma cell line, SH-SY5Y cells (2009)
  • Author(s): Murakami, K. H. Ito, M. Hagiwara, K. Yoshida1, Y. Tagawa1, N. Sasaki, A. Takagi, T. Kojima, Y. Banno, K. Tamiya-Koizumi, Y. Nozawa, T. Murate
  • Organizer: 50th International. Conference on the Bioscience of Lipids
  • Place of Presentation: Regensburg, Germany
  • Year and Date: 20090901-05
• [Presentation] スフィンゴシンキナーゼによる抗癌剤感受性の制御機構 (2009)
  • Author(s): 坂野喜子、河野早紀、竹下未希、川原さと実、中村光浩、大沢陽介、伊藤善則、土屋照雄、村手隆、野沢義則
  • Organizer: 第4回スフィンゴテラピー(STC)研究会
  • Place of Presentation: 米子
  • Year and Date: 20090717-18
• [Presentation] セラミドキナーゼのATRAによる転写調節機序の解明 (2009)
  • Author(s): 村上真史、伊藤裕美、萩原和美、吉田佳世、田川容子、佐々木法子、高木明、小嶋哲人、坂野喜子、野沢義則、村手隆
  • Organizer: 第4回スフィンゴテラピー(STC)研究会
  • Place of Presentation: 米子
  • Year and Date: 20090717-18
• [Presentation] 胆管結紮誘導性慢性肝障害モデルにおける肝細胞抗アポトーシス獲得機序の検討 (2009)
  • Author(s): 大沢陽介、永木正仁、坂野喜子、中島茂、森脇久隆、清島満
  • Organizer: 第4回スフィンゴテラピー(STC)研究会
  • Place of Presentation: 米子
  • Year and Date: 20090717-18
• [Presentation] 大腸がん細胞のスフィンゴ脂質による抗がん剤感受性の調節機構 (2009)
  • Author(s): 河野早紀、竹下未希、中村光浩、根本聡、坂野喜子、土屋照雄、伊藤善規
  • Organizer: 日本薬学会第129年会
  • Place of Presentation: 京都
  • Year and Date: 20090326-28