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图片来源：medicalxpress.com
2015年11月9日 讯 /生物谷BIOON/ –在世界范围内，肺癌引发的死亡都要多于其它癌症的死亡率，而且肺癌引发的死亡多半是因为癌症已经发生了转移；近日来自美国西北大学的科学家们通过研究首次揭示了，肌球蛋白9b（Myosin 9b）基因和肺癌肿瘤形成及癌症转移直接相关，相关研究刊登于国际著名杂志Journal of Clinical Investigation上。
Myo9b是肌球蛋白9b基因编码的蛋白，其存在于大约90%的肺癌组织样本中，而且较高水平的Myo9b蛋白预示着患者的生存率较低，研究者揭示，减少或沉默Myo9b在癌症中的表达或许可以帮助治疗遭受肺癌转移的患者。研究者Jane Wu教授表示，蛋白Myo9b表达水平的升高和肺癌的快速恶化及较差预后直接相关，而当前研究结论或可帮助开发以Myo9b为基础的癌症新型生物标志物。
此前研究者通过研究发现，一种名为SLIT的基因家族参与了乳腺癌、脑癌及胰腺癌的发展，而同中国的研究者合作研究后本文的研究者首次发现，Slit2基因可以减少肺癌模型及所有细胞培养液中肿瘤的形成和癌症转移。Wu说道，如今我们已经鉴别出了大量和肺癌发病相关的基因，然而抑制肺癌进展和转移的天然存在的基因及基因通路目前并不清楚。
因此下一步研究者将去研究可以促进Slit2抑制癌细胞迁移的基因信号通路，本文中研究者发现名为Myo9b的特殊蛋白，研究者不仅在肺癌细胞中发现了该蛋白，而且还在大量的肺癌组织中检测到了该蛋白的存在。机体中Myo9b蛋白高水平表达的患者往往会因抑制该蛋白的疗法而获益。
最后研究者总结道，本文研究为阐明肺癌扩散和转移的分子机制提供了新的希望和思路，当前的研究数据为后期开发新型的肺癌诊断技术及治疗工具提供了新的帮助。（基因宝jiyinbao.com）
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Myo9b is a key player in SLIT/ROBO-mediated lung tumor suppression.
Kong R, Yi F, Wen P, Liu J, Chen X, Ren J, Li X, Shang Y, Nie Y, Wu K, Fan D, Zhu L, Feng W, Wu JY.
Emerging evidence indicates that the neuronal guidance molecule SLIT plays a role in tumor suppression, as SLIT-encoding genes are inactivated in several types of cancer, including lung cancer; however, it is not clear how SLIT functions in lung cancer. Here, our data show that SLIT inhibits cancer cell migration by activating RhoA and that myosin 9b (Myo9b) is a ROBO-interacting protein that suppresses RhoA activity in lung cancer cells. Structural analyses revealed that the RhoGAP domain of Myo9b contains a unique patch that specifically recognizes RhoA. We also determined that the ROBO intracellular domain interacts with the Myo9b RhoGAP domain and inhibits its activity; therefore, SLIT-dependent activation of RhoA is mediated by ROBO inhibition of Myo9b. In a murine model, compared with control lung cancer cells, SLIT-expressing cells had a decreased capacity for tumor formation and lung metastasis. Evaluation of human lung cancer and adjacent nontumor tissues revealed that Myo9b is upregulated in the cancer tissue. Moreover, elevated Myo9b expression was associated with lung cancer progression and poor prognosis. Together, our data identify Myo9b as a key player in lung cancer and as a ROBO-interacting protein in what is, to the best of our knowledge, a newly defined SLIT/ROBO/Myo9b/RhoA signaling pathway that restricts lung cancer progression and metastasis. Additionally, our work suggests that targeting the SLIT/ROBO/Myo9b/RhoA pathway has potential as a diagnostic and therapeutic strategy for lung cancer.