Dataset Information

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 ?Np63? 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 ?Np63? 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 ?Np63? expression during attachment to the matrix, and decreased ?Np63? protein plays a critical role in the interaction between cancer cell clusters and the urothelium. Thus, because ?Np63? might be involved in the process of intraluminal dissemination of urothelial cancer cells, blocking the degradation of ?Np63? could be a target of therapy to prevent the dissemination of urothelial cancer.

SUBMITTER: Yoshida T

PROVIDER: S-EPMC4547408 | biostudies-literature | 2015 Jul

REPOSITORIES: biostudies-literature

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Dynamic Change in p63 Protein Expression during Implantation of Urothelial Cancer Clusters.

Yoshida Takahiro T Okuyama Hiroaki H Nakayama Masashi M Endo Hiroko H Tomita Yasuhiko Y Nonomura Norio N Nishimura Kazuo K Inoue Masahiro M

Neoplasia (New York, N.Y.) 20150701 7

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 protea ...[more]

PMID: 26297435

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Project description:Recent clinical trials reported that increasing high-density lipoprotein-cholesterol (HDL-C) levels does not improve cardiovascular outcomes. We hypothesize that HDL proteome dynamics determine HDL cardioprotective functions. In this study, we characterized proteome profiles in HDL subclasses and established their functional connection. Mouse plasma was fractionized by fast protein liquid chromatography, examined for protein, cholesterial, phospholipid and trigliceride content. Small, medium and large (S/M/L)-HDL subclasseses were collected for proteomic analysis by mass spectrometry. Fifty-one HDL proteins (39 in S-HDL, 27 in M-HDL and 29 in L-HDL) were identified and grouped into 4 functional categories (lipid metabolism, immune response, coagulation, and others). Eleven HDL common proteins were identified in all HDL subclasses. Sixteen, 3 and 7 proteins were found only in S-HDL, M-HDL and L-HDL, respectively. We established HDL protein dynamic distribution in S/M/L-HDL and developed a model of protein composition change during HDL maturation. We found that cholesterol efflux and immune response are essential functions for all HDL particles, and amino acid metabolism is a special function of S-HDL, whereas anti-coagulation is special for M-HDL. Pon1 is recruited into M/L-HDL to provide its antioxidative function. ApoE is incorporated into L-HDL to optimize its cholesterial clearance function. Next, we acquired HDL proteome data from Pubmed and identified 12 replicated proteins in human and mouse HDL particle. Finally, we extracted 3 shared top moleccular pathways (LXR/RXR, FXR/RXR and acute phase response) for all HDL particles and 5 top disease/bio-functions differentially related to S/M/L-HDL subclasses, and presented one top net works for each HDL subclass. We conclude that beside their essencial functions of cholesterol efflux and immune response, HDL aquired antioxidative and cholesterol clearance functions by recruiting Pon1 and ApoE during HDL maturation.

Dataset Information

Dynamic Change in p63 Protein Expression during Implantation of Urothelial Cancer Clusters.

Publications

Dynamic Change in p63 Protein Expression during Implantation of Urothelial Cancer Clusters.

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