title: Novel anticancer agent, SQAP, binds to focal adhesion kinase and modulates its activity.
abstract: SQAP is a novel and promising anticancer agent that was obtained by structural modifications from a natural compound. SQAP inhibits angiogenesis in vivo resulting in increased hypoxia and reduced tumor volume. In this study, the mechanism by which SQAP modifies the tumor microenvironment was revealed through the application of a T7 phage display screening. This approach identified five SQAP-binding proteins including sterol carrier protein 2, multifunctional enzyme type 2, proteasomal ubiquitin receptor, UV excision repair protein and focal adhesion kinase (FAK). All the interactions were confirmed by surface plasmon resonance analysis. Since FAK plays an important role in cell turnover and angiogenesis, the influence of SQAP on FAK was the principal goal of this study. SQAP decreased FAK phosphorylation and cell migration in human umbilical vein endothelial cells and A549 cancer cells. These findings suggest that inhibition of FAK phosphorylation works as the mechanism for the anti-angiogenesis activity of SQAP.
authors.affiliation: Department of Applied Biological Science, Faculty of Science and Technology, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan.
authors.forename: Jesus
authors.initials: J
authors.lastname: Izaguirre-Carbonell
authors.affiliation: Department of Applied Biological Science, Faculty of Science and Technology, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Kawakubo
authors.affiliation: Department of Applied Biological Science, Faculty of Science and Technology, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Murata
authors.affiliation: Laboratory of Biology, Azabu University School of Veterinary Medicine, Sagamihara 229-8501, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Tanabe
authors.affiliation: Department of Applied Biological Science, Faculty of Science and Technology, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan.
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Takeuchi
authors.affiliation: Department of Applied Biological Science, Faculty of Science and Technology, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan.
authors.forename: Tomoe
authors.initials: T
authors.lastname: Kusayanagi
authors.affiliation: Department of Applied Biological Science, Faculty of Science and Technology, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan.
authors.forename: Senko
authors.initials: S
authors.lastname: Tsukuda
authors.affiliation: Department of Applied Biological Science, Faculty of Science and Technology, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Hirakawa
authors.affiliation: Department of Applied Biological Science, Faculty of Science and Technology, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan.
authors.forename: Kazuki
authors.initials: K
authors.lastname: Iwabata
authors.affiliation: Department of Applied Biological Science, Faculty of Science and Technology, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Kanai
authors.affiliation: Department of Oral Radiation Oncology, Graduate school, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo 113-85-10, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Ohta
authors.affiliation: Department of Oral Radiation Oncology, Graduate school, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo 113-85-10, Japan.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Miura
authors.affiliation: Department of Applied Biological Science, Faculty of Science and Technology, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan.
authors.forename: Kengo
authors.initials: K
authors.lastname: Sakaguchi
authors.affiliation: Department of Applied Biological Science, Faculty of Science and Technology, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan.
authors.forename: Sachihiro
authors.initials: S
authors.lastname: Matsunaga
authors.affiliation: Laboratory of Biology, Azabu University School of Veterinary Medicine, Sagamihara 229-8501, Japan.
authors.forename: Hiroeki
authors.initials: H
authors.lastname: Sahara
authors.affiliation: Department of Applied Biological Science, Faculty of Science and Technology, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Kamisuki
authors.affiliation: Department of Applied Biological Science, Faculty of Science and Technology, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan.
authors.forename: Fumio
authors.initials: F
authors.lastname: Sugawara
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D001665:Binding Sites; D018288:Carcinoma, Small Cell / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D045643:DNA Repair Enzymes / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D051417:Focal Adhesion Kinase 1 / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D006017:Glycolipids / Q000138:chemical synthesis / Q000494:pharmacology*; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D062105:Molecular Docking Simulation; D008969:Molecular Sequence Data; D019151:Peptide Library; D064029:Peroxisomal Multifunctional Protein-2 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011485:Protein Binding; D023041:Xenograft Model Antitumor Assays
chemical_list: C500781:ADRM1 protein, human; D000970:Antineoplastic Agents; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D006017:Glycolipids; D047908:Intracellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins; D019151:Peptide Library; C513287:RAD23B protein, human; C072087:sterol carrier proteins; C000605760:sulfoquinovosylacylpropanediol; D051417:Focal Adhesion Kinase 1; C496050:PTK2 protein, human; D064029:Peroxisomal Multifunctional Protein-2; C104587:HSD17B4 protein, human; D045643:DNA Repair Enzymes