The type III inositol 1,4,5-trisphosphate receptor is associated with aggressiveness of colorectal carcinoma.
The type III inositol 1,4,5-trisphosphate receptor is associated with aggressiveness of colorectal carcinoma.
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DOI：
10.1016/j.ceca.2010.09.005
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发表时间：
2010-12
期刊：
影响因子：
4
通讯作者：
Yamaguchi K
中科院分区：
文献类型：
--
作者：
Shibao K;Fiedler MJ;Nagata J;Minagawa N;Hirata K;Nakayama Y;Iwakiri Y;Nathanson MH;Yamaguchi K
1，4，5-三磷酸肌醇受体（InsP 3R）介导上皮细胞中的Ca 2+信号并调节细胞功能，如分泌、凋亡和细胞增殖。一个或多个InsP 3R同种型的缺失与疾病过程如胆汁淤积有关。在这里，我们研究了InsP 3R亚型表达的增加是否也可能与疾病的发展有关。所有三个InsP 3R亚型的表达进行了评估，从116例结直肠癌手术切除的组织。I型和II型InsP 3R见于正常结直肠粘膜和结直肠癌，而III型InsP 3R仅见于结直肠癌。Ⅲ型InsP 3R在肿瘤边缘的表达与肿瘤浸润深度、淋巴结转移、肝转移和TNM分期有关。III型InsP 3R的高表达也与5年生存率降低相关。在CACO-2结肠癌细胞中，III型InsP 3R的shRNA敲低增强了凋亡，而受体的过表达降低了凋亡。因此，III型InsP 3R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。这些研究结果表明，以前未被认识到的作用，通过这种InsP 3R亚型的Ca 2+信号在结肠癌。
The inositol 1,4,5-trisphosphate receptor (InsP3R) mediates Ca2+ signaling in epithelia and regulates cellular 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.
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DOI：
10.1073/pnas.152571899
发表时间：
2002-07-23
影响因子：
11.1
作者：
Li, C;Fox, CJ;Thompson, CB
通讯作者：
Thompson, CB
影响因子：
4.8
作者：
Minagawa, N;Kruglov, EA;Nathanson, MH
通讯作者：
Nathanson, MH
影响因子：
3.6
作者：
FUJINO, I;YAMADA, N;MIKOSHIBA, K
通讯作者：
MIKOSHIBA, K
影响因子：
4.8
作者：
Rodrigues, Michele A.;Gomes, Dawidson A.;Nathanson, Michael H.
通讯作者：
Nathanson, Michael H.
影响因子：
4.8
作者：
Hernandez, Erick;Leite, M. Fatima;Nathanson, Michael H.
通讯作者：
Nathanson, Michael H.