LIM KINASE 1 (LIMK1) AND METASTASIS, THE SEARCH FOR LIMK1 INHIBITORS

播散性癌症与局限性疾病不同，很少能通过药物治疗治愈。我们发现LIM激酶(LIMK1)是我们实验室发现的一种蛋白，它在控制肿瘤细胞扩散能力方面发挥着重要作用，这一过程被称为转移。因此，这种蛋白成为开发新的药物疗法以防止癌症扩散的重要靶点。重要的是，我们已经证明(1)抑制LIMK1可以阻止小鼠转移性肿瘤的形成，(2)将这种蛋白引入肿瘤细胞使其更具侵袭性。此外，我们还发现，在容易在小鼠身上形成肿瘤的人类肿瘤细胞系中，LIMK1的水平要高得多。此外，测量扩散到其他器官的癌细胞中这种蛋白质的水平表明，与正常组织相比，它的水平显著升高。这项研究的目的是：(1)了解LIMK1调节肿瘤扩散和侵袭的能力是否与其控制转移的能力相关；(2)在人类肿瘤样本中检测LIMK1的水平是否与转移肿瘤的发展相关；以及(3)寻找能够抑制这种蛋白质活性的药物。这项研究的结果将具有非常重要的意义，因为LIMK1水平可能是肿瘤转移的重要标志。有可能，在肿瘤诊断时，LIMK1测量将使临床医生能够预测单个肿瘤是否会转移。其次，该蛋白是一种新的药物开发靶点。抑制这种蛋白的药物可能会阻止肿瘤的侵袭和转移能力。

Disseminated cancer, unlike the localized disease, can rarely be cured by drug therapy. We have found that LIM kinase (LIMK1), a protein that was discovered in our laboratory, plays an important role in controlling the ability of tumour cells to spread, a process called metastasis. Thus, this protein becomes an important target for the development of new drug therapies to prevent the spread of cancer. Importantly, we have demonstrated that (1) inhibiting LIMK1 blocks the formation of metastatic tumours in mice, and (2) introduction of this protein into tumour cells makes them more invasive. In addition, we find that the level of LIMK1 is much higher in human tumour cell lines that have the propensity to easily form tumours in mice. Also, measuring the level of this protein in cancer cells that spread to other organs shows that it is at significantly elevated levels when compared to normal tissue. The goals of this research are to: (1) understand whether the ability of LIMK1 to regulate tumour spreading and invasiveness correlates with its ability to control metastasis; (2) examine in human tumour samples whether the levels of LIMK1 correlate with the development of metastatic tumours; and (3) search for drugs that can inhibit the activity of this protein. The results from this research will be highly significant because LIMK1 levels are likely to be an important marker for which tumours will become metastatic. It is possible that, at the time of tumour diagnosis, LIMK1 measurements will enable the clinician to predict whether an individual tumour will become metastatic. Secondly, this protein is a novel drug development target. Drugs that inhibit this protein may block the ability of tumours to invade and metastasise.