title: Dynamic Change in p63 Protein Expression during Implantation of Urothelial Cancer Clusters.
abstract: Although the dissemination of urothelial cancer cells is supposed to be a major cause of the multicentricity of urothelial tumors, the mechanism of implantation has not been well investigated. Here, we found that cancer cell clusters from the urine of patients with urothelial cancer retain the ability to survive, grow, and adhere. By using cell lines and primary cells collected from multiple patients, we demonstrate that △Np63α protein in cancer cell clusters was rapidly decreased through proteasomal degradation when clusters were attached to the matrix, leading to downregulation of E-cadherin and upregulation of N-cadherin. Decreased △Np63α protein level in urothelial cancer cell clusters was involved in the clearance of the urothelium. Our data provide the first evidence that clusters of urothelial cancer cells exhibit dynamic changes in △Np63α expression during attachment to the matrix, and decreased △Np63α protein plays a critical role in the interaction between cancer cell clusters and the urothelium. Thus, because △Np63α might be involved in the process of intraluminal dissemination of urothelial cancer cells, blocking the degradation of △Np63α could be a target of therapy to prevent the dissemination of urothelial cancer.
authors: Department of Biochemistry, Osaka Medical Center for Cancer and Cardiovascular Diseases; Department of Urology, Osaka University Graduate School of Medicine.
authors: Takahiro
authors: T
authors: Yoshida
authors: Department of Biochemistry, Osaka Medical Center for Cancer and Cardiovascular Diseases.
authors: Hiroaki
authors: H
authors: Okuyama
authors: Department of Urology, Osaka Medical Center for Cancer and Cardiovascular Diseases.
authors: Masashi
authors: M
authors: Nakayama
authors: Department of Biochemistry, Osaka Medical Center for Cancer and Cardiovascular Diseases.
authors: Hiroko
authors: H
authors: Endo
authors: Department of Pathology, Osaka Medical Center for Cancer and Cardiovascular Diseases.
authors: Yasuhiko
authors: Y
authors: Tomita
authors: Department of Urology, Osaka University Graduate School of Medicine.
authors: Norio
authors: N
authors: Nonomura
authors: Department of Urology, Osaka Medical Center for Cancer and Cardiovascular Diseases.
authors: Kazuo
authors: K
authors: Nishimura
authors: Department of Biochemistry, Osaka Medical Center for Cancer and Cardiovascular Diseases; Department of Clinical and Experimental Pathophysiology, Osaka University Graduate School of Pharmaceutical Sciences. Electronic address: inoue-ma2@mc.pref.osaka.jp.
authors: Masahiro
authors: M
authors: Inoue
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics; D015820:Cadherins / Q000096:biosynthesis; D002448:Cell Adhesion / Q000502:physiology*; D049109:Cell Proliferation / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D004847:Epithelial Cells / Q000473:pathology; D006801:Humans; D015398:Signal Transduction / Q000502:physiology; D018874:Spheroids, Cellular; D014157:Transcription Factors / Q000096:biosynthesis*; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis*; D014556:Urine / Q000166:cytology; D014571:Urologic Neoplasms / Q000235:genetics / Q000473:pathology*; D019459:Urothelium / Q000473:pathology*
chemical_list: D014408:Biomarkers, Tumor; D015820:Cadherins; C115051:TP63 protein, human; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins