Zhang Jianliang, Hochwald Steven N
Department of Surgical Oncology, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263, United States.
Department of Surgical Oncology, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263, United States.
Pharmacol Ther. 2014 May;142(2):154-63. doi: 10.1016/j.pharmthera.2013.12.003. Epub 2013 Dec 9.
Focal adhesion kinase (FAK) plays a vital role in tumor cell proliferation, survival and migration. Altered metabolic pathways fuel rapid tumor growth by accelerating glucose, lipid and glutamine processing. Besides the mitogenic effects of FAK, evidence is accumulating supporting the association between hyper-activated FAK and aberrant metabolism in tumorigenesis. FAK can promote glucose consumption, lipogenesis, and glutamine dependency to promote cancer cell proliferation, motility, and survival. Clinical studies demonstrate that FAK-related alterations of tumor metabolism are associated with increased risk of developing solid tumors. Since FAK contributes to the malignant phenotype, small molecule inhibition of FAK-stimulated bioenergetic and biosynthetic processes can provide a novel approach for therapeutic intervention in tumor growth and invasion.
粘着斑激酶(FAK)在肿瘤细胞增殖、存活和迁移中起着至关重要的作用。代谢途径的改变通过加速葡萄糖、脂质和谷氨酰胺的代谢来推动肿瘤的快速生长。除了FAK的促有丝分裂作用外,越来越多的证据支持在肿瘤发生过程中,过度激活的FAK与异常代谢之间存在关联。FAK可促进葡萄糖消耗、脂肪生成和谷氨酰胺依赖性,从而促进癌细胞的增殖、运动和存活。临床研究表明,与FAK相关的肿瘤代谢改变与实体瘤发生风险增加有关。由于FAK促成了恶性表型,小分子抑制FAK刺激的生物能量和生物合成过程可为肿瘤生长和侵袭的治疗干预提供一种新方法。