Yalak Garif, Vogel Viola
Harvard Medical School/Harvard School of Dental Medicine, Department of Developmental Biology, Harvard University, Boston, Massachusetts, 02115; Laboratory of Applied Mechanobiology, Department of Health Sciences and Technology, ETH Zurich, Switzerland.
Cancer Med. 2015 Mar;4(3):404-14. doi: 10.1002/cam4.368. Epub 2014 Dec 14.
While small-molecule kinase inhibitors became the most prominent anticancer drugs, novel combinatorial strategies need to be developed as the fight against cancer is not yet won. We review emerging literature showing that the release of several ectokinases is significantly upregulated in body fluids from cancer patients and that they leave behind their unique signatures on extracellular matrix (ECM) proteins. Our analysis of proteomic data reveals that fibronectin is heavily phosphorylated in cancer tissues particularly within its growth factor binding sites and on domains that regulate fibrillogenesis. We are thus making the case that cancer is not only a disease of cells but also of the ECM. Targeting extracellular kinases or the extracellular signatures they leave behind might thus create novel opportunities in cancer diagnosis as well as new avenues to interfere with cancer progression and malignancy.
虽然小分子激酶抑制剂已成为最突出的抗癌药物，但由于抗癌之战尚未胜利，仍需开发新的联合治疗策略。我们回顾了最新文献，这些文献表明，几种胞外激酶在癌症患者体液中的释放显著上调，并且它们在细胞外基质（ECM）蛋白上留下了独特的印记。我们对蛋白质组学数据的分析表明，纤连蛋白在癌组织中高度磷酸化，尤其是在其生长因子结合位点以及调节纤维形成的结构域中。因此，我们认为癌症不仅是一种细胞疾病，也是一种细胞外基质疾病。靶向细胞外激酶或它们留下的细胞外印记可能会为癌症诊断创造新机会，并为干扰癌症进展和恶性肿瘤开辟新途径。
