Yilmaz Mahmut, Christofori Gerhard
Institute of Biochemistry and Genetics, Department of Biomedicine, University of Basel, Basel, Switzerland.
Cancer Metastasis Rev. 2009 Jun;28(1-2):15-33. doi: 10.1007/s10555-008-9169-0.
The metastatic process, i.e. the dissemination of cancer cells throughout the body to seed secondary tumors at distant sites, requires cancer cells to leave the primary tumor and to acquire migratory and invasive capabilities. In a process of epithelial-mesenchymal transition (EMT), besides changing their adhesive repertoire, cancer cells employ developmental processes to gain migratory and invasive properties that involve a dramatic reorganization of the actin cytoskeleton and the concomitant formation of membrane protrusions required for invasive growth. The molecular processes underlying such cellular changes are still only poorly understood, and the various migratory organelles, including lamellipodia, filopodia, invadopodia and podosomes, still require a better functional and molecular characterization. Notably, direct experimental evidence linking the formation of migratory membrane protrusions and the process of EMT and tumor metastasis is still lacking. In this review, we have summarized recent novel insights into the molecular processes and players underlying EMT on one side and the formation of invasive membrane protrusions on the other side.
转移过程,即癌细胞在全身扩散以在远处形成继发性肿瘤,要求癌细胞离开原发性肿瘤并获得迁移和侵袭能力。在上皮-间质转化(EMT)过程中,癌细胞除了改变其黏附特性外,还利用发育过程来获得迁移和侵袭特性,这涉及肌动蛋白细胞骨架的剧烈重组以及侵袭性生长所需的膜突起的形成。导致这种细胞变化的分子过程仍知之甚少,包括片状伪足、丝状伪足、侵袭性伪足和小体等各种迁移细胞器仍需要更好的功能和分子特征描述。值得注意的是,仍缺乏将迁移性膜突起的形成与EMT及肿瘤转移过程联系起来的直接实验证据。在本综述中,我们一方面总结了关于EMT潜在分子过程和相关因子的最新新见解,另一方面总结了侵袭性膜突起形成的相关见解。