{"created":"2023-06-26T11:00:56.290503+00:00","id":1535,"links":{},"metadata":{"_buckets":{"deposit":"7bb2b381-f019-4830-8e4d-60b5eee54487"},"_deposit":{"created_by":22,"id":"1535","owners":[22],"pid":{"revision_id":0,"type":"depid","value":"1535"},"status":"published"},"_oai":{"id":"oai:oist.repo.nii.ac.jp:00001535","sets":["7:200"]},"author_link":[],"item_10006_creator_3":{"attribute_name":"Author","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"Roy, Sona Rani","creatorNameLang":"en"}]}]},"item_10006_date_granted_11":{"attribute_name":"Degree Conferral Date","attribute_value_mlt":[{"subitem_dategranted":"2020-05-31"}]},"item_10006_degree_grantor_9":{"attribute_name":"Degree Conferrral Institution","attribute_value_mlt":[{"subitem_degreegrantor":[{"subitem_degreegrantor_name":"Okinawa Institute of Science and Technology Graduate University"}],"subitem_degreegrantor_identifier":[{"subitem_degreegrantor_identifier_name":"38005","subitem_degreegrantor_identifier_scheme":"kakenhi"}]}]},"item_10006_degree_name_8":{"attribute_name":"Degree","attribute_value_mlt":[{"subitem_degreename":"Doctor of Philosophy"}]},"item_10006_description_7":{"attribute_name":"Abstract","attribute_value_mlt":[{"subitem_description":"Cancer metastasis, the ability of cancer cell to change position within the tissue through migration and invasion represents the most deadly aspect of cancer. As one of the ongoing challenges in cancer therapy, it’s failed in most treatments. For example, cell surface receptor-integrin that functions as adhesion molecule is well-recognized drug target for anti-metastatic drug development. By targeting the integrin-ligand binding site, antibody, and small molecule antagonists have been commonly used. But these treatments only offer modest response rates on limited cancer types. Therefore, nanotechnology that has been widely applied in biomedical engineering is desired in the cancer metastasis treatment. Inspired by the facts that integrin density, clustering, and redistribution on cell surface are the key spatial features influencing cell motility, we intend to develop a molecular self-assembly (MSA) technology that suppresses cancer metastasis by regulating integrin spatial distribution. To achieve the goal, we designed and synthesized a library of self-assembling integrin ligands composed of 29 peptides made via conjugation of phenylalanine based hydrophobic peptide and various integrin ligands. After confirming that they self-assemble in aqueous solution, we examined these peptides in multiple cancer cell lines and screened out five peptides that exert caner-cell-specific migration. We further examined peptide 5 among the 5 peptides and observed the peptide shows inhibition on cancer invasion, spheroid growth and spreading. We explored the molecular mechanism of the peptide on migration inhibition and found the the self-assembly of the peptide forms nanostructured microdomain as nano-biointerface on cancer cell membrane. We examined the molecular consequences of the bio-nanointerface on mechanotransduction-related proteins, especially the Hippo signaling related ones. Finally, the peptide is applied in xenograft tumor models in mice to examine the efficacy of tumor suppression effect and the molecular consequences in vivo. The research work presented in the thesis is intend to establish an easy and practical strategy for anti-metastatic drug development, and illustrate how basic biochemical insights can be exploited as the basis for a nano-biointerface fabrication technology which links nanoscale protein activities to molecular biological activities to suppress metastasis.","subitem_description_language":"en","subitem_description_type":"Other"}]},"item_10006_dissertation_number_12":{"attribute_name":"Degree Referral Number","attribute_value_mlt":[{"subitem_dissertationnumber":"甲第54号"}]},"item_10006_identifier_registration":{"attribute_name":"ID登録","attribute_value_mlt":[{"subitem_identifier_reg_text":"10.15102/1394.00001397","subitem_identifier_reg_type":"JaLC"}]},"item_10006_rights_13":{"attribute_name":"Copyright Information","attribute_value_mlt":[{"subitem_rights":"© 2020 The Author."}]},"item_10006_text_24":{"attribute_name":"Exam Date","attribute_value_mlt":[{"subitem_text_value":"2020-04-16"}]},"item_10006_version_type_18":{"attribute_name":"Version Format","attribute_value_mlt":[{"subitem_version_resource":"http://purl.org/coar/version/c_970fb48d4fbd8a85","subitem_version_type":"VoR"}]},"item_access_right":{"attribute_name":"アクセス権","attribute_value_mlt":[{"subitem_access_right":"open access","subitem_access_right_uri":"http://purl.org/coar/access_right/c_abf2"}]},"item_files":{"attribute_name":"ファイル情報","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2020-12-01"}],"displaytype":"detail","filename":"Full text.pdf","filesize":[{"value":"179.8 MB"}],"format":"application/pdf","licensefree":"Creative Commons Attribution 4.0 International(https://creativecommons.org/licenses/by/4.0/)","licensetype":"license_note","mimetype":"application/pdf","url":{"label":"Full text","objectType":"fulltext","url":"https://oist.repo.nii.ac.jp/record/1535/files/Full text.pdf"},"version_id":"fa82c6b8-9936-4f18-9461-da8eec7d530f"},{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2020-06-01"}],"displaytype":"detail","filename":"Final Exam Abstract.pdf","filesize":[{"value":"42.9 kB"}],"format":"application/pdf","licensetype":"license_note","mimetype":"application/pdf","url":{"label":"Final Exam Abstract","objectType":"abstract","url":"https://oist.repo.nii.ac.jp/record/1535/files/Final Exam Abstract.pdf"},"version_id":"2c34a567-f60f-4d96-b983-a12660b15da7"}]},"item_language":{"attribute_name":"言語","attribute_value_mlt":[{"subitem_language":"eng"}]},"item_resource_type":{"attribute_name":"資源タイプ","attribute_value_mlt":[{"resourcetype":"doctoral thesis","resourceuri":"http://purl.org/coar/resource_type/c_db06"}]},"item_title":"癌遊走阻害のためのインテグリンを標的とした自己組織化ペプチドの設計","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"癌遊走阻害のためのインテグリンを標的とした自己組織化ペプチドの設計","subitem_title_language":"ja"},{"subitem_title":"Design Integrin-targeted Molecular Self-assembling Peptides for Studying Cancer Migration Inhibition","subitem_title_language":"en"}]},"item_type_id":"10006","owner":"22","path":["200"],"pubdate":{"attribute_name":"PubDate","attribute_value":"2020-06-01"},"publish_date":"2020-06-01","publish_status":"0","recid":"1535","relation_version_is_last":true,"title":["癌遊走阻害のためのインテグリンを標的とした自己組織化ペプチドの設計"],"weko_creator_id":"22","weko_shared_id":-1},"updated":"2023-08-31T02:52:31.331495+00:00"}