Metastasis tumor-associated protein 2 enhances metastatic behavior and is associated with poor outcomes in estrogen receptor-negative breast cancer.
Metastasis tumor-associated protein 2 enhances metastatic behavior and is associated with poor outcomes in estrogen receptor-negative breast cancer.
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DOI：
10.1007/s10549-013-2709-5
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发表时间：
2013-10
影响因子：
3.8
通讯作者：
Fuqua, Suzanne A. W.
中科院分区：
文献类型：
--
作者：
Covington, Kyle R.;Brusco, Lauren;Barone, Ines;Tsimelzon, Anna;Selever, Jennifer;Corona-Rodriguez, Arnoldo;Brown, Powel;Kumar, Rakesh;Hilsenbeck, Susan G.;Fuqua, Suzanne A. W.
乳腺癌的转移仍然是一个主要的临床问题。先前与转移有关的一个基因家族是转移性肿瘤相关（MTA）家族，其中MTA1增强和MTA3抑制癌症转移。我们之前已经发现MTA2增强雌激素受体α (ERα)乳腺癌的锚定不依赖性生长，并且与其他基因结合，作为ERα阳性乳腺癌的预测性生物标志物。因此，我们假设MTA2促进乳腺癌的进展。为了验证这一点，研究了mta2过表达和载体对照转染er α-阴性乳腺癌细胞的细胞生长、软琼脂集落形成、迁移和体内转移。通过Rho途径调节细胞间相互作用、粘附和信号传导的途径也被研究。Rho激酶（ROCK）抑制剂对Rho通路的抑制作用在mta2过表达细胞的软琼脂集落形成和运动实验中进行了评估。在回顾性分析中，MTA2表达与不良预后标志物相关，MTA2水平与早期复发风险增加相关。在体外和体内，MTA2过表达与增强的转移和调节细胞间相互作用的途径有关。最关键的是，mta2增强的运动性可以通过抑制Rho通路信号传导而被阻断。我们提出了一项新的发现，MTA2定义了er α阴性患者的一个亚群，其预后特别差。
Metastasis remains a major clinical problem in breast cancer. One family of genes previously linked with metastasis is the metastasis tumor associated (MTA) family, with members MTA1 enhancing and MTA3 inhibiting cancer metastasis. We have previously found that MTA2 enhances anchorage-independent growth in estrogen receptor α (ERα) breast cancers, and, in combination with other genes, performed as a predictive biomarker in ERα-positive breast cancer. We therefore hypothesized that MTA2 enhances breast cancer progression. To test this, cell growth, soft-agar colony formation, migration, and in vivo metastasis were examined in MTA2-overexpressing and vector control transfected ERα-negative breast cancer cells. Pathways regulating cell-cell interaction, adhesion, and signaling through the Rho pathway were also investigated. Effects of the inhibition of the Rho pathway using a Rho Kinase (ROCK) inhibitor were assessed in soft agar colony formation and motility assays in MTA2-overexpressing cells. MTA2 expression was associated with poor prognostic markers, and levels of MTA2 were associated with increased risk of early recurrence in retrospective analyses. MTA2 overexpression was associated with enhanced metastasis, and pathways regulating cell-cell interactions in vitro and in vivo. Most critically, MTA2-enhanced motility could be blocked by inhibiting Rho pathway signaling. We present the novel finding that MTA2 defined a subset of ERα-negative patients with a particularly poor outcome.
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影响因子：
8
作者：
Barone, I.;Iacopetta, D.;Covington, K. R.;Cui, Y.;Tsimelzon, A.;Beyer, A.;Ando, S.;Fuqua, S. A. W.
通讯作者：
Fuqua, S. A. W.
影响因子：
2.9
作者：
Amano, Mutsuki;Nakayama, Masanori;Kaibuchi, Kozo
通讯作者：
Kaibuchi, Kozo
影响因子：
2.9
作者：
Liu, Guang Jian;Wang, Zheng Jun;Zeng, Yan Jun
通讯作者：
Zeng, Yan Jun
影响因子：
10.3
作者：
Barone, Ines;Brusco, Lauren;Fuqua, Suzanne A. W.
通讯作者：
Fuqua, Suzanne A. W.
影响因子：
3.8
作者：
Bauer, Katrina;Parise, Carol;Caggiano, Vincent
通讯作者：
Caggiano, Vincent