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JCI：siRNA筛选发现促乳腺癌转移关键因子

2015-03-23 佚名 生物谷

乳腺癌siRNA
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近日，著名国际期刊JCI在线发表了荷兰莱顿大学研究人员的一项最新研究成果，他们利用小干扰RNA对H1299细胞内与细胞迁移有关的基因进行了筛选，发现了一些与肿瘤细胞迁移速度和持续性有关的基因，并发现了与乳腺癌病人肿瘤转移密切相关的SRPK1基因或可成为乳腺癌药物治疗的潜在靶点，因此具有重要意义。   肿瘤细胞迁移是癌细胞扩散的一个重要过程，而这一过程主要通过信号介导的细胞骨架和细

近日，著名国际期刊JCI在线发表了荷兰莱顿大学研究人员的一项最新研究成果，他们利用小干扰RNA对H1299细胞内与细胞迁移有关的基因进行了筛选，发现了一些与肿瘤细胞迁移速度和持续性有关的基因，并发现了与乳腺癌病人肿瘤转移密切相关的SRPK1基因或可成为乳腺癌药物治疗的潜在靶点，因此具有重要意义。
 
肿瘤细胞迁移是癌细胞扩散的一个重要过程，而这一过程主要通过信号介导的细胞骨架和细胞黏附基质的重塑来进行调控。研究人员利用小干扰RNA筛选技术对具有迁移性的H1299细胞的1500多个编码激酶/磷酸酶和迁移黏附相关蛋白的基因进行了筛选，发现了影响肿瘤细胞迁移速度和持续性的基因。
 
研究人员通过肿瘤细胞迁移实验，证实了30个候选基因可能会影响细胞迁移过程，其中8个基因与乳腺癌病人的肿瘤侵袭性具有相关性，ITGB3BP,MAP3K8,NEK2,SHC1等4个基因最具有可预测性。研究人员通过检测调控细胞迁移的相关基因发现一种叫做SRPK1的基因在基底乳腺癌中具有高表达，与乳腺癌进展最具相关性。进一步研究发现，高表达的SRPK1与乳腺癌的恶性程度有关，其倾向于促进乳腺癌细胞发生肺转移和脑转移。研究人员在两个乳腺癌转移小鼠模型中敲低SRPK1，能够抑制癌细胞向肺，肝脏和脾脏等远端器官的转移，并能抑制黏着斑的重排。
 
这项研究为人们了解肿瘤细胞迁移的机制提供了重要帮助，同时表明SRPK1或许可成为限制乳腺癌转移的潜在药物靶点，具有重要意义。

原始出处：

Wies van Roosmalen,et al.Tumor cell migration screen identifies SRPK1 as breast cancer metastasis determinant[J].J Clin Invest.March 16,2015.doi:10.1172/JCI74440.

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    2015-10-21 caobinglei8079

    #JCI#

    0

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    2015-10-17 tcm99hq

    #关键因子#

    0

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    2015-03-25 12498ebem23暂无昵称

    #siRNA#

    0

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    2015-03-25 ms6747015003810650

    #筛选#

    0

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    2015-03-25 linagood

    #癌转移#

    0

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目前，绝大多数乳腺癌属于激素受体阳性乳腺癌，如接近60%~75%患者为雌激素受体阳性（ER+），65%患者为孕激素受体阳性（PgR+）。而辅助内分泌治疗几乎对所有ER+和（或）PgR+乳腺癌有效，已在发达国家和发展中国家患者中得到广泛应用。 近10年，他莫昔芬治疗5年被公认为激素受体阳性乳腺癌辅助内分泌治疗的标准治疗方案。近期，芳香化酶抑制剂成为绝经后女性患者替代他莫昔芬或他莫昔芬后续治