Dataset Information

Tumor selective proteotoxicity of verteporfin inhibits colon cancer progression independent of YAP1

ABSTRACT: Verteporfin (VP) inhibts colon cancer growth in vivo and in cell lines by inducing high molecular weight oligomerization of proteins. The antitumor effect of VP is independent of its YAP inhibitor activity. Tumor hypoxia contributes partly to antitumor effect of VP by impairing clearance of VP-induced high molecular weight aggregates.

INSTRUMENT(S): Orbitrap Fusion ETD

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Colon Epithelial Cell

DISEASE(S): Colon Cancer

SUBMITTER: Sadeesh Ramakrishnan

LAB HEAD: Yatrik M. Shah

PROVIDER: PXD002793 | Pride | 2015-10-14

REPOSITORIES: Pride

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Publications

Tumor-selective proteotoxicity of verteporfin inhibits colon cancer progression independently of YAP1.

Zhang Huabing H Ramakrishnan Sadeesh K SK Triner Daniel D Centofanti Brook B Maitra Dhiman D Győrffy Balázs B Sebolt-Leopold Judith S JS Dame Michael K MK Varani James J Brenner Dean E DE Fearon Eric R ER Omary M Bishr MB Shah Yatrik M YM

Science signaling 20151006 397

Yes-associated protein 1 (YAP1) is a transcriptional coactivator in the Hippo signaling pathway. Increased YAP1 activity promotes the growth of tumors, including that of colorectal cancer (CRC). Verteporfin, a drug that enhances phototherapy to treat neovascular macular degeneration, is an inhibitor of YAP1. We found that verteporfin inhibited tumor growth independently of its effects on YAP1 or the related protein TAZ in genetically or chemically induced mouse models of CRC, in patient-derived ...[more]

PMID: 26443705

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Project description:Studies centered at the intersection of embryogenesis and carcinogenesis have identified striking parallels involving signaling pathways that modulate both developmental and neoplastic processes. In the prostate, reciprocal interactions between epithelium and stroma are known to influence neoplasia and also exert morphogenic effects via the urogenital sinus mesenchyme. In this study, we sought to determine molecular relationships between aspects of normal prostate development and prostate carcinogenesis. We first characterized the gene expression program associated with key points of murine prostate organogenesis spanning the initial in utero induction of prostate budding through maturity. We identified a highly reproducible temporal program of gene expression that partitioned according to the broad developmental stages of prostate induction, branching morphogenesis, and secretory differentiation. Comparisons of gene expression profiles of murine prostate cancers arising in the context of genetically engineered alterations in the Pten tumor suppressor and Myc oncogene identified significant associations between the profile of branching morphogenesis and both cancer models. Further, the expression of genes comprising the branching morphogenesis program, such as PRDX4, SLC43A1, and DNMT3A, was significantly altered in human neoplastic prostate epithelium. These results indicate that components of normal developmental processes are active in prostate neoplasia and provide further rationale for exploiting molecular features of organogenesis to understand cancer phenotypes. Whole male UGS (E14.5, E15.5, E16.5, and E17.5) or separated prostate lobes (P7, P30, and DP90) were dissected from C57BL6/J mice and snap frozen in liquid nitrogen. For each biological replication, we pooled 3 to 10 mice representing one or two litters. RNA from pools of UGS or specific prostate lobes (vp, ap, and dlp) was prepared using the Qiagen RNeasy Mini kit. We included an on-column DNaseI treatment to remove contaminating DNA. Before RNA amplification, we combined equal quantities of RNA from vp, ap, and dlp for the postnatal prostate samples. We amplified 1 ug of total RNA from each sample through one round using the Arcturus RiboAmp kit. For the E14.5 UGS reference sample, a second round of amplification was done to provide enough RNA for all microarrays. Each developmental sample was hybridized against the E14.5 UGS reference sample with a dye swap, for a total of 42 arrays. Warning: the normalized data for this study which was made public on December 1, 2009, was swapped for some samples. All normalized data has now been corrected as of February 25, 2010. Raw data was not affected.

Dataset Information

Tumor selective proteotoxicity of verteporfin inhibits colon cancer progression independent of YAP1

Publications

Tumor-selective proteotoxicity of verteporfin inhibits colon cancer progression independently of YAP1.

Similar Datasets

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