Dissemination of cancer cells from the primary tumor and their spread to distant sites of the body is the leading cause of mortality in metastatic cancer patients. Metastatic cancer cells invade surrounding tissues and blood vessels by forming F-actin-rich protrusions known as invadopodia, which degrade the extracellular matrix and enable invasion of tumor cells through it. Invadopodia have now been observed in vivo, and recent evidence demonstrates direct molecular links between assembly of invadopodia and cancer metastasis in both mouse models and in human patients. While significant progress has been achieved in the last decade in understanding the molecular mechanisms and signaling pathways regulating invadopodia formation and function, the application of this knowledge to development of prognostic and therapeutic approaches for cancer metastasis has not been discussed before. Here, we provide a detailed overview of current prognostic markers and tests for cancer metastasis and discuss their advantages, disadvantages, and their predicted efficiency. Using bioinformatic patient database analysis, we demonstrate, for the first time, a significant correlation between invadopodia-associated genes to breast cancer metastasis, suggesting that invadopodia could be used as both a prognostic marker and as a therapeutic target for blocking cancer metastasis. We include here a novel network interaction map of invadopodia-associated proteins with currently available inhibitors, demonstrating a central role for the recently identified EGFR-Pyk2-Src-Arg-cortactin invadopodial pathway, to which re-purposing of existent inhibitors could be used to block breast cancer metastasis. We then present an updated overview of current cancer-related clinical trials, demonstrating the negligible number of trials focusing on cancer metastasis. We also discuss the difficulties and complexity of performing cancer metastasis clinical trials, and the possible development of anti-metastasis drug resistance when using a prolonged preventive treatment with invadopodia inhibitors. This review presents a new perspective on invadopodia-mediated tumor invasiveness and may lead to the development of novel prognostic and therapeutic approaches for cancer metastasis.

癌细胞从原发肿瘤中的扩散及其扩散到身体的远处是转移性癌症患者死亡的主要原因。转移性癌细胞通过形成称为Invadopodia的富含F-肌动蛋白的突起侵入周围的组织和血管，该突起会降解细胞外基质并使肿瘤细胞能够通过其侵袭。现在已经在体内观察到了Invadopodia，最近的证据表明，在小鼠模型和人类患者中，侵袭足病的组装与癌症转移之间都存在直接的分子联系。在过去十年中，在了解调节尺v足形成和功能的分子机制和信号传导途径方面已取得了重大进展，但此知识在癌症转移的预后和治疗方法开发中的应用尚未见过讨论。在这里，我们提供了有关癌症转移的当前预后标志物和测试的详细概述，并讨论了它们的优缺点和预测效率。使用生物信息学的患者数据库分析，我们首次证明了invadopodia相关基因与乳腺癌转移之间的显着相关性，提示侵染足病既可以用作预后标志物，又可以作为阻断癌症转移的治疗靶标。我们在这里包括了一个与Invadopodia相关蛋白与目前可用的抑制剂的新型网络相互作用图，这表明了最近鉴定的EGFR-Pyk2-Src-Arg-cortactin侵足途径的中心作用，可以利用现有抑制剂的重新用途来达到这一目的。阻止乳腺癌转移。然后，我们介绍了当前与癌症相关的临床试验的最新概述，证明了针对癌症转移的试验数量可忽略不计。我们还讨论了进行癌症转移临床试验的困难和复杂性，以及在长期使用invadopodia抑制剂进行预防性治疗时抗转移耐药性的可能发展。