StarD13 is a tumor suppressor in breast cancer that regulates cell motility and invasion.

StarD13 is a tumor suppressor in breast cancer that regulates cell motility and invasion.
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DOI:
10.3892/ijo.2014.2330
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发表时间:
2014-05
影响因子:
5.2
通讯作者:
El-Sibai M
El-Sibai M
中科院分区:
医学2区
文献类型:
--
作者:
Hanna S;Khalil B;Nasrallah A;Saykali BA;Sobh R;Nasser S;El-Sibai M

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乳腺癌是世界各地妇女最常诊断的癌症之一。一般来说,肿瘤的侵袭性越强,它生长得越快,转移的可能性就越大。小GTP结合蛋白(GTP酶)的Rho亚家族成员在乳腺癌细胞运动和转移中发挥核心作用。鸟嘌呤核苷酸交换因子(GEF)、GTP酶激活蛋白(GAP)和鸟嘌呤核苷酸解离抑制剂(GDIs)调节活性GTP结合状态和非活性GDP结合状态之间的转换。我们研究了StarD 13的作用,StarD 13是一种最近发现的Rho-GAP,它特异性抑制RhoA和Cdc 42的功能。我们的目的是研究其在乳腺癌增殖和转移中的作用。采用免疫组化法检测不同级别肿瘤组织中Rho-GAP的表达水平。我们观察到,虽然与正常组织相比,StarD 13表达水平在癌组织中降低,但随着肿瘤级别的增加而增加。这与以下事实相一致:尽管StarD 13确实是我们乳腺癌细胞中的肿瘤抑制因子,正如其对细胞增殖的影响所示,但它是癌细胞运动所必需的。事实上,StarD 13敲低导致细胞运动性的抑制,细胞不能脱离它们的尾巴并向前移动。我们的研究首次描述了一种在癌症运动中起积极作用的肿瘤抑制因子。
Breast cancer is one of the most commonly diagnosed cancers in women around the world. In general, the more aggressive the tumor, the more rapidly it grows and the more likely it metastasizes. Members of the Rho subfamily of small GTP-binding proteins (GTPases) play a central role in breast cancer cell motility and metastasis. The switch between active GTP-bound and inactive GDP-bound state is regulated by guanine nucleotide exchange factors (GEFs), GTPase-activating proteins (GAPs) and guanine-nucleotide dissociation inhibitors (GDIs). We studied the role of StarD13, a recently identified Rho-GAP that specifically inhibits the function of RhoA and Cdc42. We aimed to investigate its role in breast cancer proliferation and metastasis. The levels of expression of this Rho-GAP in tumor tissues of different grades were assayed using immunohistochemistry. We observed that, while the level of StarD13 expression decreases in cancer tissues compared to normal tissues, it increases as the grade of the tumor increased. This was consistent with the fact that although StarD13 was indeed a tumor suppressor in our breast cancer cells, as seen by its effect on cell proliferation, it was needed for cancer cell motility. In fact, StarD13 knockdown resulted in an inhibition of cell motility and cells were not able to detach their tail and move forward. Our study describes, for the first time, a tumor suppressor that plays a positive role in cancer motility.
Rho GTPases控制细胞运动过程中的极性,突出和粘附。
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