Loss of TACSTD2 contributed to squamous cell carcinoma progression through attenuating TAp63-dependent apoptosis.
Loss of TACSTD2 contributed to squamous cell carcinoma progression through attenuating TAp63-dependent apoptosis.
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TACSTD2 的缺失通过减弱 TAp63 依赖性细胞凋亡导致鳞状细胞癌进展
DOI：
10.1038/cddis.2014.96
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发表时间：
2014-03-20
影响因子：
9
通讯作者：
中科院分区：
文献类型：
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肿瘤相关钙信号转导子2（TACSTD 2）是一种钙信号转导子，广泛表达于皮肤、食管和宫颈等多种器官的复层鳞状上皮。尽管据报道TACSTD 2在许多上皮肿瘤中过表达，这增加了人们将其用作癌症治疗分子靶点的兴趣，但TACSTD 2在鳞状细胞癌（SCC）致癌过程中的作用在很大程度上尚不清楚且存在争议。为了探讨TACSTD 2的作用，分析了TACSTD 2在正常和SCC组织中的时空表达。我们的数据表明，Tacstd2的表达和膜定位与分层上皮细胞的稳态密切相关，而TACSTD2的丢失在从宫颈、食管、头颈部收集的低分化SCC组织中被鉴定。TACSTD 2的逐渐丢失与SCC的逐步进展相关。与这些体内观察结果一致，我们的数据表明，Tacstd2表达的抑制显着抑制化疗试剂诱导的细胞凋亡，和TACSTD2调节凋亡基因的表达，通过P63含有反式激活结构域（TAp63）。这些结果表明TACSTD 2的缺失可以通过TAp63减弱化疗药物诱导的细胞凋亡而促进SCC的进展和治疗抵抗，并且TACSTD 2可以用作SCC病理分级的标志物。
Tumor-associated calcium signal transducer 2 (TACSTD2), a calcium signal transducer, is universally expressed in stratified squamous epithelia of many organs, including skin, esophagus and cervix. Although TACSTD2, was reported to be overexpressed in many epithelial tumors, which has increased interest in using it as a molecular target for cancer therapy, the role of TACSTD2 in carcinogenesis of squamous cell carcinoma (SCC) is largely unclear and controversial. To explore the role of TACSTD2, temporal-spatial expression of TACSTD2 was analyzed in both normal and SCC tissues. Our data demonstrate that Tacstd2 expression and membrane localization are tightly associated with stratified epithelial homeostasis, while loss of TACSTD2 was identified in poorly differentiated SCC tissues collected from cervix, esophagus, head and neck. Gradual loss of TACSTD2 was correlated with stepwise progression of SCC. Consistent with these in vivo observations, our data show that inhibition of Tacstd2 expression significantly inhibited chemotherapeutic reagent-induced apoptosis, and TACSTD2 regulated apoptotic gene expression through P63 containing the transactivation domain (TAp63). These findings indicated that loss of TACSTD2 could promote SCC progression and treatment resistance through attenuating chemotherapeutic reagent-induced apoptosis through TAp63, and TACSTD2 could be used as a marker for pathological grading of SCC.
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DOI：
10.1038/nrm3175
发表时间：
2011-08-23
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
通讯作者：
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DOI：
10.1242/dev.021964
发表时间：
2008-08
期刊：
Development (Cambridge, England)
影响因子：
--
作者：
Wan H;Luo F;Wert SE;Zhang L;Xu Y;Ikegami M;Maeda Y;Bell SM;Whitsett JA
通讯作者：
Whitsett JA
影响因子：
3.6
作者：
Micallef, Ludovic;Belaubre, Francoise;Simon, Alain
通讯作者：
Simon, Alain
影响因子：
10.5
作者：
Koster, MI;Kim, S;Roop, DR
通讯作者：
Roop, DR
影响因子：
30.8
作者：
Herron, BJ;Liddell, RA;Siracusa, LD
通讯作者：
Siracusa, LD