Hess Angela R, Hendrix Mary J C
Children's Memorial Research Center, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60614-3394, USA.
Cell Cycle. 2006 Mar;5(5):478-80. doi: 10.4161/cc.5.5.2518. Epub 2006 Mar 1.
Focal adhesion kinase (FAK) mediates myriad cellular functions and has been found to be overexpressed in numerous human cancers. We recently explored the role of FAK in promoting the aggressive phenotype of melanoma cells, characterized by increased invasion, migration, and vasculogenic mimicry (VM) potential. We found FAK to be phosphorylated on its key tyrosine residues (397 and 576) in aggressive melanoma cells cultured on a three-dimensional type 1 collagen matrix in vitro, as well as in radial and vertical growth phase melanomas in situ. Furthermore, expressing FAK-related non-kinase (FRNK) in melanoma cells directly resulted in the inhibition of the aggressive phenotype, as demonstrated by decreased invasion, migration and VM potential, in part by blocking an Erk1/2 mediated signaling pathway. Additional data indicated that increased FAK activity may promote cellular proliferation and anchorage independent growth of aggressive melanoma. Together these observations implicate FAK as a promoter of the aggressive melanoma phenotype, thereby identifying a rational target for therapeutic intervention of malignant melanoma.
粘着斑激酶（FAK）介导多种细胞功能，并且已发现在多种人类癌症中过表达。我们最近探讨了FAK在促进黑色素瘤细胞侵袭性表型中的作用，该表型的特征是侵袭、迁移和血管生成拟态（VM）能力增强。我们发现，在体外三维I型胶原基质上培养的侵袭性黑色素瘤细胞以及原位放射状和垂直生长期黑色素瘤中，FAK在其关键酪氨酸残基（397和576）上发生磷酸化。此外，在黑色素瘤细胞中表达FAK相关非激酶（FRNK）直接导致侵袭性表型受到抑制，表现为侵袭、迁移和VM能力降低，部分原因是阻断了Erk1/2介导的信号通路。其他数据表明，增加的FAK活性可能促进侵袭性黑色素瘤的细胞增殖和锚定非依赖性生长。这些观察结果共同表明FAK是侵袭性黑色素瘤表型的促进因子，从而确定了恶性黑色素瘤治疗干预的合理靶点。
