1 Department of Biomedical Engineering, Northwestern University, Evanston, Illinois; and.
Am J Respir Cell Mol Biol. 2014 Jan;50(1):1-6. doi: 10.1165/rcmb.2013-0314TR.
There is an accumulation of evidence in the literature demonstrating the integral role of vimentin intermediate filaments (IFs) in the progression of lung cancers. Vimentin IF proteins have been implicated in many aspects of cancer initiation and progression, including tumorigenesis, epithelial-to-mesenchymal transition (EMT), and the metastatic spread of cancer. Specifically, vimentin IFs have been recognized as an essential component regulating EMT, major signal transduction pathways involved in EMT and tumor progression, cell migration and invasion, the positioning and anchorage of organelles, such as mitochondria, and cell-cell and cell-substrate adhesion. In tumorgenesis, vimentin forms a complex with 14-3-3 and beclin 1 to inhibit autophagy via an AKT-dependent mechanism. Vimentin is a canonical marker of EMT, and recent evidence has shown it to be an important regulator of cellular motility. Transcriptional regulation of vimentin through hypoxia-inducible factor-1 may be a potential driver of EMT. Finally, vimentin regulates 14-3-3 complexes and controls various intracellular signaling and cell cycle control pathways by depleting the availability of free 14-3-3. There are many exciting advances in our understanding of the complex role of vimentin IFs in cancer, pointing to the key role vimentin IFs may play in tumor progression.
越来越多的文献证据表明波形蛋白中间丝（IF）在肺癌的进展中起着重要作用。波形蛋白 IF 蛋白与癌症的发生和发展的许多方面有关，包括肿瘤发生、上皮间质转化（EMT）和癌症的转移扩散。具体来说，波形蛋白 IF 已被认为是调节 EMT 的必需成分，是 EMT 和肿瘤进展、细胞迁移和侵袭、细胞器（如线粒体）的定位和锚定、细胞-细胞和细胞-基质黏附的主要信号转导途径的重要组成部分。在肿瘤发生中，波形蛋白与 14-3-3 和 beclin 1 形成复合物，通过 AKT 依赖性机制抑制自噬。波形蛋白是 EMT 的典型标志物，最近的证据表明它是细胞运动的重要调节剂。通过缺氧诱导因子-1 对波形蛋白进行转录调控可能是 EMT 的一个潜在驱动因素。最后，波形蛋白通过耗尽游离 14-3-3 的可用性来调节 14-3-3 复合物，并控制各种细胞内信号和细胞周期控制途径。我们对波形蛋白 IF 在癌症中的复杂作用的理解有了许多令人兴奋的进展，这表明波形蛋白 IF 在肿瘤进展中可能发挥关键作用。
