S Marquard1, S Thomann2, S M E Weiler2, C Sticht3, N Gretz3, P Schirmacher2, K Breuhahn2. 1. Pathologisches Institut Heidelberg, Universität Heidelberg, Im Neuenheimer Feld 224, 69120, Heidelberg, Deutschland. simone.marquard@med.uni-heidelberg.de. 2. Pathologisches Institut Heidelberg, Universität Heidelberg, Im Neuenheimer Feld 224, 69120, Heidelberg, Deutschland. 3. Medizinische Fakultät Mannheim, Medical Research Center, Universität Heidelberg, Mannheim, Deutschland.
Abstract
BACKGROUND: The transcriptional coactivator yes-associated protein (YAP) is a strong oncogene in liver cancer development. OBJECTIVES: To investigate if and how YAP-induced paracrine-acting factors are regulated in hepatocytes and liver cancer cells. MATERIAL AND METHODS: Transcriptome analysis and proteomics of murine wildtype and YAP-transgenic hepatocytes were performed to identify paracrine-acting proteins. Molecular and biochemical techniques were used to examine the mechanisms of YAP-dependent gene regulation. Gene expression data from HCC (hepatocellular carcinoma) patients was evaluated. RESULTS: Several YAP-dependent, secreted factors (e. g. CXCL10, GDF15, PDGFB) were identified. YAP regulates these factors through transcription factors of the TEAD (TEA domain) protein family. Moreover, the dysregulation of the YAP-target genes is often associated with poor HCC patient prognosis. CONCLUSIONS: YAP induces the expression of paracrine-acting factors that may affect the tumor microenvironment and therefore support carcinogenesis. This multicellular network could allow the development of novel and specific perturbation approaches.
BACKGROUND: The transcriptional coactivator yes-associated protein (YAP) is a strong oncogene in liver cancer development. OBJECTIVES: To investigate if and how YAP-induced paracrine-acting factors are regulated in hepatocytes and liver cancer cells. MATERIAL AND METHODS: Transcriptome analysis and proteomics of murine wildtype and YAP-transgenic hepatocytes were performed to identify paracrine-acting proteins. Molecular and biochemical techniques were used to examine the mechanisms of YAP-dependent gene regulation. Gene expression data from HCC (hepatocellular carcinoma) patients was evaluated. RESULTS: Several YAP-dependent, secreted factors (e. g. CXCL10, GDF15, PDGFB) were identified. YAP regulates these factors through transcription factors of the TEAD (TEA domain) protein family. Moreover, the dysregulation of the YAP-target genes is often associated with poor HCC patient prognosis. CONCLUSIONS:YAP induces the expression of paracrine-acting factors that may affect the tumor microenvironment and therefore support carcinogenesis. This multicellular network could allow the development of novel and specific perturbation approaches.
Authors: Yi Liu-Chittenden; Bo Huang; Joong Sup Shim; Qian Chen; Se-Jin Lee; Robert A Anders; Jun O Liu; Duojia Pan Journal: Genes Dev Date: 2012-06-07 Impact factor: 11.361
Authors: Fernando D Camargo; Sumita Gokhale; Jonathan B Johnnidis; Dongdong Fu; George W Bell; Rudolf Jaenisch; Thijn R Brummelkamp Journal: Curr Biol Date: 2007-11-01 Impact factor: 10.834