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However, the cellular and molecular mechanisms underlying the effect of synphilin-1 in PD remain poorly understood. The present study aimed to elucidate the molecular function of synphilin-1 using integrated transcriptomic and proteomic in silico analyses, followed by in vitro validation. Synphilin-1 overexpression enhanced cell viability and attenuated pathways associated with cell death. Among the identified regulatory molecules, p53 emerged as a key mediator linking synphilin-1 to suppression of anoikis. Notably, p53 expression demonstrated predominant nuclear localisation in midbrain tissues of individuals with PD. These findings suggest that synphilin-1 promotes cell survival by suppressing p53-mediated anoikis. This regulatory relationship could be crucial for understanding neuroprotective or pathological mechanisms in PD.<\/jats:p>","DOI":"10.1042\/bsr20260173","type":"journal-article","created":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T10:45:55Z","timestamp":1788518755000},"update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Integrated omics-driven discovery reveals synphilin-1-mediated anoikis resistance through p53 down-regulation"],"prefix":"10.1042","volume":"46","author":[{"given":"Seok\u00a0Gi","family":"Kim","sequence":"first","affiliation":[{"name":"1Department of Physiology, Ajou University School of Medicine, 164 World Cup-ro, Suwon 16499, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ye\u00a0Eun","family":"Sim","sequence":"additional","affiliation":[{"name":"2Department of Biomedical Sciences, BK21 R&E Initiative for Advanced Precision Medicine, Graduate School of Ajou University, 164 World cup-ro, Suwon 16499, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdurazak\u00a0Aman","family":"Ketebo","sequence":"additional","affiliation":[{"name":"3Department of Mechanical Engineering, Sungkyunkwan University, 2066 Seobu-ro, Suwon 16419, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji\u00a0Su","family":"Hwang","sequence":"additional","affiliation":[{"name":"1Department of Physiology, Ajou University School of Medicine, 164 World Cup-ro, Suwon 16499, Republic of Korea"},{"name":"4Department of Molecular Science and Technology, Ajou University, 206 World cup-ro, Suwon 16499, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nimisha\u00a0Pradeep","family":"George","sequence":"additional","affiliation":[{"name":"4Department of Molecular Science and Technology, Ajou University, 206 World cup-ro, Suwon 16499, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong\u00a0Eun","family":"Jang","sequence":"additional","affiliation":[{"name":"1Department of Physiology, Ajou University School of Medicine, 164 World Cup-ro, Suwon 16499, Republic of Korea"},{"name":"4Department of Molecular Science and Technology, Ajou University, 206 World cup-ro, Suwon 16499, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minjun","family":"Kwon","sequence":"additional","affiliation":[{"name":"1Department of Physiology, Ajou University School of Medicine, 164 World Cup-ro, Suwon 16499, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sungsu","family":"Park","sequence":"additional","affiliation":[{"name":"3Department of Mechanical Engineering, Sungkyunkwan University, 2066 Seobu-ro, Suwon 16419, Republic of Korea"},{"name":"5Institute of Quantum Biophysics (IQB), Sungkyunkwan University, 2066 Seobu-ro, Suwon 16419, Republic of Korea"},{"name":"6Department of MetaBioHealth, Sungkyunkwan University, 2066 Seobu-ro, Suwon 16419, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jung-Soon","family":"Mo","sequence":"additional","affiliation":[{"name":"2Department of Biomedical Sciences, BK21 R&E Initiative for Advanced Precision Medicine, Graduate School of Ajou University, 164 World cup-ro, Suwon 16499, Republic of Korea"},{"name":"7Institute of Medical Science, Ajou University School of Medicine, 164 World cup-ro, Suwon 16499, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1299-9478","authenticated-orcid":false,"given":"Gwang","family":"Lee","sequence":"additional","affiliation":[{"name":"1Department of Physiology, Ajou University School of Medicine, 164 World Cup-ro, Suwon 16499, Republic of Korea"},{"name":"4Department of Molecular Science and Technology, Ajou University, 206 World cup-ro, Suwon 16499, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2026,9,18]]},"reference":[{"key":"2026091804170351400_B1","doi-asserted-by":"publisher","first-page":"110","DOI":"10.1038\/8820","article-title":"Synphilin-1 associates with alpha-synuclein and promotes the formation of cytosolic inclusions","volume":"22","author":"Engelender","year":"1999","journal-title":"Nat. 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