The role of InsP3 receptor expression in colorectal cancer patients and its relation to metastasis and neo-adjuvant chemotherapy

InsP3受体表达在结直肠癌患者中的作用及其与转移和新辅助化疗的关系

• 批准号: 20591598
• 负责人: HIRATA Keiji
• 金额: $ 2.91万
• 依托单位: University of Occupational and Environmental Health, Japan
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2008
• 资助国家: 日本
• 起止时间: 2008 至 2010
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-20591598/
• 关键词: カルシウムシグナリング; IP3レセプター; 大腸癌; 細胞増殖; アポトーシス; イノシトール3リン酸受容体; 抗癌剤

The inositol 1,4,5-trisphosphate receptor (InsP3R) mediates Ca2+ signaling in epithelia and regulates cel- lular functions such as secretion, apoptosis and cell proliferation. Loss of one or more InsP3R isoform has been implicated in disease processes such as cholestasis. Here we examined whether gain of expression of InsP3R isoforms also may be associated with development of disease. Expression of all three InsP3R isoforms was evaluated in tissue from colorectal carcinomas surgically resected from 116 patients. Type I and II InsP3Rs were seen in both normal colorectal mucosa and colorectal cancer, while type III InsP3R was observed only in colorectal cancer. Type III InsP3R expression in the advancing margins of tumors correlated with depth of invasion, lymph node metastasis, liver metastasis, and TNM stage. Heavier expression of type III InsP3R also was associated with decreased 5-year survival. shRNA knockdown of type III InsP3R in CACO-2 colon cancer cells enhanced apoptosis, while over-expression of the receptor decreased apoptosis. Thus, type III InsP3R becomes expressed in colon cancer, and its expression level is directly related to aggressiveness of the tumor, which may reflect inhibition of apoptosis by the receptor. These findings suggest a previously unrecognized role for Ca2+ signaling via this InsP3R isoform in colon cancer.

肌醇1,4,5-三磷酸受体（InsP3R）介导上皮细胞中的Ca2+信号传导并调节细胞功能，例如分泌、凋亡和细胞增殖。一种或多种 InsP3R 同工型的丢失与胆汁淤积等疾病过程有关。在这里，我们检查了 InsP3R 亚型表达的增加是否也可能与疾病的发展有关。对 116 名患者手术切除的结直肠癌组织中所有三种 InsP3R 亚型的表达进行了评估。 I型和II型InsP3R在正常结直肠粘膜和结直肠癌中均可见，而III型InsP3R仅在结直肠癌中观察到。肿瘤进展边缘中的 III 型 InsP3R 表达与浸润深度、淋巴结转移、肝转移和 TNM 分期相关。 III 型 InsP3R 的较高表达也与 5 年生存率降低相关。 CACO-2 结肠癌细胞中 III 型 InsP3R 的 shRNA 敲除增强了细胞凋亡，而受体的过度表达则减少了细胞凋亡。因此，III型InsP3R在结肠癌中表达，其表达水平与肿瘤的侵袭性直接相关，这可能反映了受体对细胞凋亡的抑制。这些发现表明，通过这种 InsP3R 亚型的 Ca2+ 信号传导在结肠癌中具有以前未被认识到的作用。

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The type III inositol 1,4,5-trisphosphate receptor is associated with aggressiveness of colorectal carcinoma.

• DOI: 10.1016/j.ceca.2010.09.005
• 发表时间: 2010-12
• 期刊: Cell calcium
• 影响因子: 4
• 作者: Shibao K;Fiedler MJ;Nagata J;Minagawa N;Hirata K;Nakayama Y;Iwakiri Y;Nathanson MH;Yamaguchi K
• 通讯作者: Yamaguchi K

大腸癌における3型イノシトール3リン酸レセプター発現は悪性度の指標となる

结直肠癌中3型肌醇三磷酸受体表达是恶性肿瘤的指标

• 发表时间: 2008
• 作者: Mizobe T;Ogata Y;Murakami H;Akagi Y;Ishibashi N;Mori S;Sasatomi T;Shirouzu K;柴尾和徳
• 通讯作者: 柴尾和徳