The involvement of sphingolipid metabolism in anti cancer drug sensitivity of malignant cells

鞘脂代谢参与恶性细胞抗癌药物敏感性

• 批准号: 23590667
• 负责人: MURATE Takashi
• 金额: $ 3.49万
• 依托单位: Nagoya University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2013
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23590667/
• 关键词: sphingolipid; metabolic enzyme; gene expression; anti-cancer drug; human cancer cell lines; SPHK1; Friend cell; c-Myb; chemical differentiation; human colon cancer cell; CD44; S1P receptor 2; ERK pathway; 国際情報交換; NSmase2; ATRA; MCF-7細胞株

In the first year, we analyzed the mechanism of GAP43 expression during GDNF treatment of a neuronal cel line, TGW. Our analysis revealed that GDNF induced SPHK1 expression through RET receptor, followed by S1P secretion and S1P1/3 receptor activation. We further found that GAP43 expression was due to the increased CREB transcription factor binding to the GAP43 5'-promoter region.Next, we analyzed the regulatory mechanism of neutral sphingomyelinase 2 and neutral ceramidase with all trans retinoid acid (ATRA). Our analysis revealed that activated Sp1 transcription factor and decreased GATA2 were responsive for the observed changes in treated MCF-7 and SH-SY5Y cells, respectively.In the third year, we analyzed the mechanism of high SPHK1 expression of mouse Friend cells. We found that c-MYB is responsible for this overepression and that chemical inducer, HMBA, rapidly decreased SPHK1 expression, which is at least partially responsible for this terminal differentiation process.

在第一年，我们分析了GDNF处理神经细胞系TGW时GAP43表达的机制。我们的分析显示GDNF通过RET受体诱导SPHK1表达，随后S1P分泌和S1P1/3受体激活。我们进一步发现，GAP43的表达是由于CREB转录因子与GAP43 5'-启动子区域结合增加所致。接下来，我们分析了全反式维甲酸（ATRA）对中性鞘磷脂酶2和中性神经酰胺酶的调控机制。我们的分析显示，Sp1转录因子的激活和GATA2的减少分别对MCF-7和SH-SY5Y细胞的变化有响应。第三年，我们分析了小鼠Friend细胞中SPHK1高表达的机制。我们发现c-MYB负责这种过表达，而化学诱导剂HMBA迅速降低SPHK1的表达，这至少部分负责这种终端分化过程。

项目成果

Sphingosine kinase 1 expression is downregulated during differentiation of Friend cells due to decreased c-MYB.

由于 c-MYB 减少，鞘氨醇激酶 1 表达在 Friend 细胞分化过程中下调。

• DOI: 10.1016/j.bbamcr.2013.01.001
• 发表时间: 2013
• 期刊: Biochimica et Biophysica Acta -Molecular Cell Research
• 作者: Mizutani N;Kobayashi M;Sobue S;Ichihara M;Ito H;Tanaka K;Iwaki S,Fujii S,Ito Y;Tamiya-Koizumi K;Takagi A;Kojima T;Naoe T;Suzuki M;Nakamura M;Banno Y;Nozawa Y;Murate T.
• 通讯作者: Murate T.

アンドロジェン反応性ヒト前立腺がん細胞株LNCaPにおける酸性セラミダーゼ発現調節機序

雄激素反应性人前列腺癌细胞系LNCaP中酸性神经酰胺酶表达的调控机制

• 发表时间: 2012
• 作者: 東田修二;大野彩;高橋祐介;奥橋佑基;伊藤真以;Toru Takano;登勉;井上みなみら
• 通讯作者: 井上みなみら

Hybrid liposomes affect cellular lipids

混合脂质体影响细胞脂质

• 发表时间: 2012
• 期刊: Bioorg Med Chem Lett
• 影响因子: 2.7
• 作者: Hiroyuki Yasui;Yutaro Natsume;and Yutaka Yoshikawa;Cao K. et al.
• 通讯作者: Cao K. et al.

C-Myb is the major regulator of sphingosine kinase 1 expression of Friend cells

C-Myb 是 Friend 细胞鞘氨醇激酶 1 表达的主要调节因子

• 发表时间: 2012
• 作者: Ohyama Yoshiaki;Kurabayashi Masahiko;Mizutani N. et al.
• 通讯作者: Mizutani N. et al.

Sphk 1 of Friend cells was decreased by HMBA

HMBA 降低 Friend 细胞的 Sphk 1

• 作者: Yamada;H.;Takano;T.;Kihara;M.;Hirokaw,a M.;Yoshida;H.;Watanabe;M.;Iwatani;Y.;Hidaka;Y.;.Miyauchi;A;小林 美沙ら
• 通讯作者: 小林 美沙ら