Large scale exome sequencing studies have ＇revealed regions of the genome, which contribute to the castrate resistant prostate cancer （CRPC） phenotype.1-3 Such studies have identified mutations in genes, which may ...Large scale exome sequencing studies have ＇revealed regions of the genome, which contribute to the castrate resistant prostate cancer （CRPC） phenotype.1-3 Such studies have identified mutations in genes, which may have diagnostic/prognostic potential, or which may be targeted therapeutically. Two of these genes include the androgen receptor （AR） and speckle-type POZ protein （SPOP） genes. However, the findings from these exome sequencing studies can only be translated therapeutically once the functional consequences of these mutations have been determined. Here, we highlight the recent study by An et al.4 which investigated the functional effects of mutations in the SPOP gene that were identified in the aforementioned exome sequencing studies, particnlarly in the context of SPOP-mediated degradation of the AR.展开更多
Whether and how garlic-derived S-allylmercaptocysteine(SAMC) inhibits hepatocellular carcinoma(HCC) is largely unknown. In the current study, the role of low-density lipoprotein receptor(LDLR)-related protein 6(LRP6) ...Whether and how garlic-derived S-allylmercaptocysteine(SAMC) inhibits hepatocellular carcinoma(HCC) is largely unknown. In the current study, the role of low-density lipoprotein receptor(LDLR)-related protein 6(LRP6) in HCC progression and the anti-HCC mechanism of SAMC was examined in clinical sample, cell model and xenograft/orthotopic mouse models. We demonstrated that SAMC inhibited cell proliferation and tumorigenesis, while induced apoptosis of human HCC cells without influencing normal hepatocytes. SAMC directly interacted with Wnt-pathway co-receptor LRP6 on the cell membrane. LRP6 was frequently over-expressed in the tumor tissue of human HCC patients(66.7% of 48 patients) and its overexpression only correlated with the over-expression of β-catenin, but not with age, gender, tumor size, stage and metastasis. Deficiency or over-expression of LRP6 in hepatoma cells could partly mimic or counteract the anti-tumor properties of SAMC, respectively. In vivo administration of SAMC significantly suppressed the growth of Huh-7 xenograft/orthotopic HCC tumor without causing undesirable side effects. In addition, stable down-regulation of LRP6 in Huh-7 facilitated the anti-HCC effects of SAMC. In conclusion, LRP6 can be a potential therapeutic target of HCC. SAMC is a promising specific anti-tumor agent for treating HCC subtypes with Wnt activation at the hepatoma cell surface.展开更多
文摘Large scale exome sequencing studies have ＇revealed regions of the genome, which contribute to the castrate resistant prostate cancer （CRPC） phenotype.1-3 Such studies have identified mutations in genes, which may have diagnostic/prognostic potential, or which may be targeted therapeutically. Two of these genes include the androgen receptor （AR） and speckle-type POZ protein （SPOP） genes. However, the findings from these exome sequencing studies can only be translated therapeutically once the functional consequences of these mutations have been determined. Here, we highlight the recent study by An et al.4 which investigated the functional effects of mutations in the SPOP gene that were identified in the aforementioned exome sequencing studies, particnlarly in the context of SPOP-mediated degradation of the AR.
基金supported by Foundation of Pearl River Science and Technology New Star (grant number 201506010087)Basic Research Fund of Shenzhen City (JCYJ20150402111430633) to Jia Xiao+7 种基金Health Medical Research Fund (HMRF,No. 12133881)General Research Fund and Small Project FundingUniversity Research Committee,The University of Hong Kong. to George L.TipoeNational Natural Science Foundation of China (No. 81570552)National Program on Key Basic Research Project of China (973 Program,2014CB542205)Funds of Leading Talents of Guangdong (2013)Programme of Introducing Talents of Discipline to Universities (B14036) to Kwok-Fai SoNational Health and Medical Research Council (1031221 & 1031228) to Ming-Tat Ling
文摘Whether and how garlic-derived S-allylmercaptocysteine(SAMC) inhibits hepatocellular carcinoma(HCC) is largely unknown. In the current study, the role of low-density lipoprotein receptor(LDLR)-related protein 6(LRP6) in HCC progression and the anti-HCC mechanism of SAMC was examined in clinical sample, cell model and xenograft/orthotopic mouse models. We demonstrated that SAMC inhibited cell proliferation and tumorigenesis, while induced apoptosis of human HCC cells without influencing normal hepatocytes. SAMC directly interacted with Wnt-pathway co-receptor LRP6 on the cell membrane. LRP6 was frequently over-expressed in the tumor tissue of human HCC patients(66.7% of 48 patients) and its overexpression only correlated with the over-expression of β-catenin, but not with age, gender, tumor size, stage and metastasis. Deficiency or over-expression of LRP6 in hepatoma cells could partly mimic or counteract the anti-tumor properties of SAMC, respectively. In vivo administration of SAMC significantly suppressed the growth of Huh-7 xenograft/orthotopic HCC tumor without causing undesirable side effects. In addition, stable down-regulation of LRP6 in Huh-7 facilitated the anti-HCC effects of SAMC. In conclusion, LRP6 can be a potential therapeutic target of HCC. SAMC is a promising specific anti-tumor agent for treating HCC subtypes with Wnt activation at the hepatoma cell surface.
