Significance of heterogeneous Twist2 expression in human breast cancers.
Significance of heterogeneous Twist2 expression in human breast cancers.
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DOI：
10.1371/journal.pone.0048178
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Liu Z
中科院分区：
文献类型：
--
作者：
Mao Y;Zhang N;Xu J;Ding Z;Zong R;Liu Z
Twist 2（Dermo 1）介导上皮间质转化（EMT），促进肿瘤侵袭甚至转移。然而，EMT在乳腺癌进展中的参与备受争议，部分原因是临床观察显示大多数人乳腺癌转移灶表达E-钙粘蛋白并保持其上皮形态。Twist 2在体内参与乳腺癌EMT的分子机制仍然知之甚少。我们通过Western blot和组织芯片检测了Twist 2在人乳腺癌中的表达模式，并通过共聚焦显微镜、细胞分级等方法分析了Twist 2的细胞定位。Twist 2在乳腺癌中的表达显著增加。胞浆型Twist 2阳性表达的癌细胞主要位于原发癌和淋巴结转移癌的肿瘤中心，而胞核型Twist 2阳性表达的癌细胞则明显缺失E-cadherin，并在乳腺导管癌的浸润前沿检测到。此外，异位稳定表达Twist 2被发现定位于癌细胞的细胞质中。总的来说，这些数据表明细胞质Twist 2的上调与人类乳腺癌中的肿瘤组织学类型和肿瘤转移相关。Twist 2的差异细胞分布可能与肿瘤进展相关。在原发癌和淋巴转移的肿瘤中心的癌细胞中的胞质Twist 2有助于维持上皮癌特征，其在非侵袭性状态下表达E-cadherin，而在癌症侵袭前沿的核Twist 2激活EMT以剥夺肿瘤细胞的上皮性质，从而促进侵袭和转移。这些发现表明，Twist 2在肿瘤中的异质性表达可能与肿瘤进展有功能联系。
Twist2 (Dermo1) has been shown to mediate the epithelial-mesenchymal transition (EMT) to promote tumor invasion and even metastasis. However, the involvement of EMT in breast cancer progression is highly debated, partially due to clinical observations showing that the majority of human breast carcinoma metastases express E-cadherin and maintain their epithelial morphology. The molecular mechanism by which Twist2 participates in EMT of breast cancer in vivo remains poorly understood. We examined Twist2 expression pattern in human breast carcinomas by western blot and tissue microarray, and analyzed Twist2 cellular localization by confocal microscopy, cell fractionation and other approaches. Twist2 expression was significantly increased in breast cancer. Cytoplasmic Twist2 positive cancer cells expressing E-cadherin on the cellular membrane were mainly located at tumor center of primary carcinomas and lymph metastases, while cancer cells with nuclear Twist2 clearly showed loss of E-cadherin and were detected at the invasive front in ductal breast carcinomas. In addition, ectopically stable-expressed Twist2 was found to localize in the cytoplasm of cancer cells. Collectively, these data indicate that upregulation of cytoplasmic Twist2 is correlated with tumor histological type and tumor metastasis in human breast cancers. The differential cellular distribution of Twist2 may be associated with tumor progression. The cytoplasmic Twist2 in cancer cells at tumor center of primary carcinomas and lymph metastases contributes to the maintenance of epithelial cancer characteristics expressing E-cadherin in a noninvasive state, while the nuclear Twist2 at the cancer invasion front activates EMT to deprive epithelial property of neoplastic cells, thus facilitating invasion and metastasis. These findings suggest that heterogeneous expression of Twist2 in tumors may have a functional link to tumor progression.
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影响因子：
5.6
作者：
Storci, Gianluca;Sansone, Pasquale;Mari, Sara;D'uva, Gabriele;Tavolari, Simona;Guarnieri, Tiziana;Taffurelli, Mario;Ceccarelli, Claudio;Santini, Donatella;Chieco, Pasquale;Marcu, Kenneth B.;Bonafe, Massimiliano
通讯作者：
Bonafe, Massimiliano
DOI：
10.1111/j.1582-4934.2008.00540.x
发表时间：
2009-08-01
影响因子：
5.3
作者：
Song, Gang;Ouyang, Gaoliang;Hu, Tianhui
通讯作者：
Hu, Tianhui
Twist2通过促进上皮-间质转化和癌症干细胞样细胞自我更新促进乳腺癌进展
影响因子：
8
作者：
Fang, X.;Cai, Y.;Ouyang, G.
通讯作者：
Ouyang, G.
影响因子：
50.3
作者：
Ansieau, Stephane;Bastid, Jeremy;Puisieux, Alain
通讯作者：
Puisieux, Alain
影响因子：
11.2
作者：
Casas E;Kim J;Bendesky A;Ohno-Machado L;Wolfe CJ;Yang J
通讯作者：
Yang J