The Ca 2+-binding protein of the EF-hand type,S100B,exerts both intracellular and extracellular regulatory activities.As an intracellular regulator,S100B is involved in the regulation of energy metabolism,transcriptio...The Ca 2+-binding protein of the EF-hand type,S100B,exerts both intracellular and extracellular regulatory activities.As an intracellular regulator,S100B is involved in the regulation of energy metabolism,transcription,protein phosphorylation,cell proliferation,survival,differentiation and motility,and Ca 2+ homeostasis,by interacting with a wide array of proteins(i.e.,enzymes,enzyme substrates,cytoskeletal subunits,scaffold/adaptor proteins,transcription factors,ubiquitin E3 ligases,ion channels) in a restricted number of cell types.As an extracellular signal,S100B engages the pattern recognition receptor,receptor for advanced glycation end-products(RAGE),on immune cells as well as on neuronal,astrocytic and microglial cells,vascular smooth muscle cells,skeletal myoblasts and cardiomyocytes.However,RAGE may not be the sole receptor activated by S100B,the protein being able to enhance bFGF-FGFR1 signaling by interacting with FGFR1-bound bFGF in particular cell types.Moreover,extracellular effects of S100B vary depending on its local concentration.Increasing evidence suggests that at the concentration found in extracellular fluids in normal physiological conditions and locally upon acute tissue injury,which is up to a few nM levels,S100B exerts trophic effects in the central and peripheral nervous system and in skeletal muscle tissue thus participating in tissue homeostasis.The present commentary summarizes results implicating intracellular and extracellular S100B in tissue development,repair and regeneration.展开更多
Pancreatic cancer is a devastating disease with the worst prognosis among all the major human malignancies. The propensity to rapidly metastasize contributes signifi- cantly to the highly aggressive feature of pancrea...Pancreatic cancer is a devastating disease with the worst prognosis among all the major human malignancies. The propensity to rapidly metastasize contributes signifi- cantly to the highly aggressive feature of pancreatic cancer. The molecular mechanisms underlying this remain elusive, and proteins involved in the control of pancreatic cancer cell motility are not fully characterized. In this study, we find that histone deacetylase 6 （HDAC6）, a member of the class II HDAC family, is highly expres- sed at both protein and mRNA levels in human pancre- atic cancer tissues. HDAC6 does not obviously affect pancreatic cancer cell proliferation or cell cycle pro- gression. Instead, it significantly promotes the motility of pancreatic cancer cells. Further studies reveal that HDAC6 interacts with cytoplasmic linker protein 170 （CLIP-170） and that these two proteins function together to stimulate the migration of pancreatic cancer cells. These findings provide mechanistic insight into the progression of pancreatic cancer and suggest HDAC6 as a potential target for the management of this malignancy.展开更多
Background To investigate the differential expression levels of thymosin β10 (Tβ10) and the corresponding changes of actin filament organization in human tumor cell lines with different metastatic potential.Methods ...Background To investigate the differential expression levels of thymosin β10 (Tβ10) and the corresponding changes of actin filament organization in human tumor cell lines with different metastatic potential.Methods Four groups of nine human tumor cell lines with different metastatic potential were analyzed for the amount of Tβ10 mRNAs by Northern blot and for their peptide expression levels by immunohistochemistry. The filamentous actin (F-actin) was observed by staining of TRITC-phalloidin to detect changes in actin organization.Results In comparison with non-/weakly metastatic counterparts, Tβ10 was upregulated in highly metastatic human lung cancer, malignant melanoma and breast cancer cell lines. Staining of TRITC-phalloidin revealed less actin bundles, a fuzzy network of shorter filaments and some F-actin aggregates in the highly metastatic tumor cells. Meanwhile, the actin filaments were robust and orderly arranged in the non-/weakly metastatic cancer cell lines.Conclusion Tβ10 levels correlate positively with the metastatic capacity in human tumors currently examined. The increasing metastatic potential of tumor cells is accompanied by a loss of F-actin, poorly arranged actin skeleton organizations and presence of F-actin aggregates. There is a consistent correlation between the elevated Tβ10 expression and the disrupted actin skeleton.展开更多
目的通过转录组测序,探讨毗邻锌指结构域的溴结构域蛋白1A(bromodomain adjacent to zinc finger domain 1A,BAZ1A)在肝癌和子宫颈癌中促癌机制的共同点。方法在肝癌和子宫颈癌转录组测序结果中使用“DESeq2”包进行筛选肝癌组差异表达...目的通过转录组测序,探讨毗邻锌指结构域的溴结构域蛋白1A(bromodomain adjacent to zinc finger domain 1A,BAZ1A)在肝癌和子宫颈癌中促癌机制的共同点。方法在肝癌和子宫颈癌转录组测序结果中使用“DESeq2”包进行筛选肝癌组差异表达基因(different expression genes,DEGs)和子宫颈癌组DEGs。肝癌组DEGs与子宫颈癌组DEGs取交集获得共有DEGs。通过基因本体论(gene ontology,GO)、京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)对以上3组DEGs相关的功能及通路进行分析。采用STRING数据库对上述3组DEGs进行蛋白质互作(protein-protein interaction,PPI)网络的富集分析,并使用Cytoscape软件筛选出各组DEGs中的核心基因。结果得到肝癌组DEGs为294个,子宫颈癌组DEGs为5662个,共有DEGs为170个。肝癌组DEGs、子宫颈癌组DEGs和共有DEGs都富集到的KEGG通路包括细胞外基质-受体相互作用通路、焦点黏附通路。肝癌组DEGs和子宫颈癌组DEGs都显著富集的GO条目包括细胞运动、生物黏附。PPI网络分析得到肝癌组核心基因为H4簇状组蛋白5(H4 clustered histone 5,H4C5)、H4簇状组蛋白14(H4 clustered histone 14,H4C14),子宫颈癌组核心基因分化簇44(cluster of differentiation,CD44)、激太原1(kininogen 1,KNG1)、圆盘大MAGUK支架蛋白4(discs large MAGUK scaffold protein 4,DLG4),共有组核心基因为H2A簇状组蛋白18(H2A clustered histone 18,H2AC18)。结论在肝癌和子宫颈癌中,BAZ1A都可以通过影响癌细胞运动、迁移的能力,发挥促癌作用。展开更多
基金Supported by Ministero dell'Università e della Ricerca,No. PRIN 2007LNKSYS,No.2007AWZTHH_004 and No.2009WBFZYM_002Association Fran aise contre les Myopathies,No. Project 12992+1 种基金Associazione Italiana per la Ricerca sul Cancro,No. Project 6021Fondazione Cassa di Risparmio di Perugia,No. 2007.0218.020,No.2009.020.0021 and No.2012.0241.021
文摘The Ca 2+-binding protein of the EF-hand type,S100B,exerts both intracellular and extracellular regulatory activities.As an intracellular regulator,S100B is involved in the regulation of energy metabolism,transcription,protein phosphorylation,cell proliferation,survival,differentiation and motility,and Ca 2+ homeostasis,by interacting with a wide array of proteins(i.e.,enzymes,enzyme substrates,cytoskeletal subunits,scaffold/adaptor proteins,transcription factors,ubiquitin E3 ligases,ion channels) in a restricted number of cell types.As an extracellular signal,S100B engages the pattern recognition receptor,receptor for advanced glycation end-products(RAGE),on immune cells as well as on neuronal,astrocytic and microglial cells,vascular smooth muscle cells,skeletal myoblasts and cardiomyocytes.However,RAGE may not be the sole receptor activated by S100B,the protein being able to enhance bFGF-FGFR1 signaling by interacting with FGFR1-bound bFGF in particular cell types.Moreover,extracellular effects of S100B vary depending on its local concentration.Increasing evidence suggests that at the concentration found in extracellular fluids in normal physiological conditions and locally upon acute tissue injury,which is up to a few nM levels,S100B exerts trophic effects in the central and peripheral nervous system and in skeletal muscle tissue thus participating in tissue homeostasis.The present commentary summarizes results implicating intracellular and extracellular S100B in tissue development,repair and regeneration.
文摘Pancreatic cancer is a devastating disease with the worst prognosis among all the major human malignancies. The propensity to rapidly metastasize contributes signifi- cantly to the highly aggressive feature of pancreatic cancer. The molecular mechanisms underlying this remain elusive, and proteins involved in the control of pancreatic cancer cell motility are not fully characterized. In this study, we find that histone deacetylase 6 （HDAC6）, a member of the class II HDAC family, is highly expres- sed at both protein and mRNA levels in human pancre- atic cancer tissues. HDAC6 does not obviously affect pancreatic cancer cell proliferation or cell cycle pro- gression. Instead, it significantly promotes the motility of pancreatic cancer cells. Further studies reveal that HDAC6 interacts with cytoplasmic linker protein 170 （CLIP-170） and that these two proteins function together to stimulate the migration of pancreatic cancer cells. These findings provide mechanistic insight into the progression of pancreatic cancer and suggest HDAC6 as a potential target for the management of this malignancy.
基金This work was supported by the National Science Foundation of China ( No. 30170363 ) Key Project on Science and Technology of Chinese Ministry of Education ( No. 01003 ) the Major State Basic Research Development Program of China (No. 2002CB513105 )
文摘Background To investigate the differential expression levels of thymosin β10 (Tβ10) and the corresponding changes of actin filament organization in human tumor cell lines with different metastatic potential.Methods Four groups of nine human tumor cell lines with different metastatic potential were analyzed for the amount of Tβ10 mRNAs by Northern blot and for their peptide expression levels by immunohistochemistry. The filamentous actin (F-actin) was observed by staining of TRITC-phalloidin to detect changes in actin organization.Results In comparison with non-/weakly metastatic counterparts, Tβ10 was upregulated in highly metastatic human lung cancer, malignant melanoma and breast cancer cell lines. Staining of TRITC-phalloidin revealed less actin bundles, a fuzzy network of shorter filaments and some F-actin aggregates in the highly metastatic tumor cells. Meanwhile, the actin filaments were robust and orderly arranged in the non-/weakly metastatic cancer cell lines.Conclusion Tβ10 levels correlate positively with the metastatic capacity in human tumors currently examined. The increasing metastatic potential of tumor cells is accompanied by a loss of F-actin, poorly arranged actin skeleton organizations and presence of F-actin aggregates. There is a consistent correlation between the elevated Tβ10 expression and the disrupted actin skeleton.
文摘目的通过转录组测序,探讨毗邻锌指结构域的溴结构域蛋白1A(bromodomain adjacent to zinc finger domain 1A,BAZ1A)在肝癌和子宫颈癌中促癌机制的共同点。方法在肝癌和子宫颈癌转录组测序结果中使用“DESeq2”包进行筛选肝癌组差异表达基因(different expression genes,DEGs)和子宫颈癌组DEGs。肝癌组DEGs与子宫颈癌组DEGs取交集获得共有DEGs。通过基因本体论(gene ontology,GO)、京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)对以上3组DEGs相关的功能及通路进行分析。采用STRING数据库对上述3组DEGs进行蛋白质互作(protein-protein interaction,PPI)网络的富集分析,并使用Cytoscape软件筛选出各组DEGs中的核心基因。结果得到肝癌组DEGs为294个,子宫颈癌组DEGs为5662个,共有DEGs为170个。肝癌组DEGs、子宫颈癌组DEGs和共有DEGs都富集到的KEGG通路包括细胞外基质-受体相互作用通路、焦点黏附通路。肝癌组DEGs和子宫颈癌组DEGs都显著富集的GO条目包括细胞运动、生物黏附。PPI网络分析得到肝癌组核心基因为H4簇状组蛋白5(H4 clustered histone 5,H4C5)、H4簇状组蛋白14(H4 clustered histone 14,H4C14),子宫颈癌组核心基因分化簇44(cluster of differentiation,CD44)、激太原1(kininogen 1,KNG1)、圆盘大MAGUK支架蛋白4(discs large MAGUK scaffold protein 4,DLG4),共有组核心基因为H2A簇状组蛋白18(H2A clustered histone 18,H2AC18)。结论在肝癌和子宫颈癌中,BAZ1A都可以通过影响癌细胞运动、迁移的能力,发挥促癌作用。
