title: Ectokinases as novel cancer markers and drug targets in cancer therapy.
abstract: 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.
authors.affiliation: 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.
authors.forename: Garif
authors.initials: G
authors.lastname: Yalak
authors.forename: Viola
authors.initials: V
authors.lastname: Vogel
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000037:antagonists & inhibitors* / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism; D006801:Humans; D009369:Neoplasms / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism; D010744:Phosphoric Monoester Hydrolases / Q000037:antagonists & inhibitors; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011494:Protein Kinases / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases; C034454:ectoprotein kinase; D010744:Phosphoric Monoester Hydrolases
keywords: Cancer marker; drug design; ectokinases; exokinases; extracellular matrix; extracellular phosphorylation; extracellular protein kinase; personalized medicine