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An extractable collagenase from crustacean hepatopancreas 总被引:5,自引:0,他引:5
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M Teodorczyk S Kleber D Wollny J P Sefrin B Aykut A Mateos P Herhaus I Sancho-Martinez O Hill C Gieffers J Sykora W Weichert C Eisen A Trumpp M R Sprick F Bergmann T Welsch A Martin-Villalba 《Cell death and differentiation》2015,22(7):1192-1202
Cancer stem cells (CSCs) have been implicated in the initiation and maintenance of tumour growth as well as metastasis. Recent reports link stemness to epithelial–mesenchymal transition (EMT) in cancer. However, there is still little knowledge about the molecular markers of those events. In silico analysis of RNA profiles of 36 pancreatic ductal adenocarcinomas (PDAC) reveals an association of the expression of CD95 with EMT and stemness that was validated in CSCs isolated from PDAC surgical specimens. CD95 expression was also higher in metastatic pancreatic cells than in primary PDAC. Pharmacological inhibition of CD95 activity reduced PDAC growth and metastasis in CSC-derived xenografts and in a murine syngeneic model. On the mechanistic level, Sck was identified as a novel molecule indispensable for CD95''s induction of cell cycle progression. This study uncovers CD95 as a marker of EMT and stemness in PDAC. It also addresses the molecular mechanism by which CD95 drives tumour growth and opens tantalizing therapeutic possibilities in PDAC.Recent analysis of the cellular heterogeneity within the tumour mass revealed the existence of cells that share characteristics with stem cells of the tissue of origin.1 These cells are responsible for the tumour''s resistance to current therapies and therefore provide new perspectives in cancer treatment. Cancer stem cells (CSCs) or tumour-initiating cells (TICs) are characterized by their self-renewal and differentiation capacity, which are assessed by their ability to generate a heterogeneous tumour in immunocompromised mice in serial transplantations.2 In pancreatic cancer, those properties were initially shown by cells expressing CD24, CD44 and ESA (epithelial surface antigen).3Pancreatic cancer is the fourth leading cause of cancer-related death in the United States of America.4 The highly malignant phenotype of pancreatic ductal adenocarcinoma (PDAC) results from aggressive invasion and early metastatic potential. Epithelial–mesenchymal transition (EMT) is considered to be the first step of metastatic spread. During this process, the tumour cells master the ability to detach from their neighbours and gain motile and invasive properties enabling them to spread via blood or lymph vessels.5 As cells undergo EMT, they lose their epithelial features including sheet-like architecture, polarity and E-cadherin expression and gradually gain motility and expression of mesenchymal markers such as N-cadherin, fibronectin and vimentin. Recent studies have uncovered a link between the EMT and the acquisition of stem cell characteristics.6, 7 Most growth factors such as TGF-β, HGF, EGF, IGF and FGF are known to trigger EMT.8 Interestingly, there is growing evidence that the so-called ‘death receptor'' CD95 (Fas/Apo-1) behaves like a growth factor receptor in cancer cells.9, 10, 11CD95 was first discovered as the initiator of programmed cell death by forming death-inducing signalling complex (DISC, including Fas-associated death domain, FADD and caspase-8/10) upon stimulation with CD95 ligand (CD95L).12 However, mitogen-activated protein kinases (MAPKs), leading to p38, JNK or extracellular signal-regulated kinase (ERK) 1/2 activation, were also reported to be driven by CD95.13, 14 In glioblastoma multiforme (GBM), CD95-induced migration depends on the formation of the so-called phosphatidyl-inositol 3-kinase (PI3K) activation complex (PAC),11, 12 consisting of the Src family kinase (SFK), Yes and p85, the regulatory subunit of PI3K. PAC components, however, differ between cell types, encompassing also other SFKs or the Syk tyrosine kinase.15, 16Here, we show that the expression of CD95 increases in primary PDACs as compared with non-tumour-bearing pancreas and is higher in metastatic pancreatic cells than in primary PDAC. In CSCs isolated from primary PDAC surgical specimens, the expression of CD95 positively correlates with EMT markers. We also identified Sck as the molecular link between CD95 and activation of the PI3K and MAPK pathways. Neutralization of the CD95L reduces PDAC growth and metastasis. The present study defines CD95 and its downstream signalling pathway components as new targets for PDAC therapy. 相似文献
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Copeland A Spring S Göker M Schneider S Lapidus A Del Rio TG Tice H Cheng JF Chen F Nolan M Bruce D Goodwin L Pitluck S Ivanova N Mavrommatis K Ovchinnikova G Pati A Chen A Palaniappan K Land M Hauser L Chang YJ Jeffries CC Meincke L Sims D Brettin T Detter JC Han C Chain P Bristow J Eisen JA Markowitz V Hugenholtz P Kyrpides NC Klenk HP Lucas S 《Standards in genomic sciences》2009,1(1):29-37
Desulfomicrobium baculatum is the type species of the genus Desulfomicrobium, which is the type genus of the family Desulfomicrobiaceae. It is of phylogenetic interest because of the isolated location of the family Desulfomicrobiaceae within the order Desulfovibrionales. D. baculatum strain X(T) is a Gram-negative, motile, sulfate-reducing bacterium isolated from water-saturated manganese carbonate ore. It is strictly anaerobic and does not require NaCl for growth, although NaCl concentrations up to 6% (w/v) are tolerated. The metabolism is respiratory or fermentative. In the presence of sulfate, pyruvate and lactate are incompletely oxidized to acetate and CO(2). Here we describe the features of this organism, together with the complete genome sequence and annotation. This is the first completed genome sequence of a member of the deltaproteobacterial family Desulfomicrobiaceae, and this 3,942,657 bp long single replicon genome with its 3494 protein-coding and 72 RNA genes is part of the Genomic Encyclopedia of Bacteria and Archaea project. 相似文献
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Clum A Nolan M Lang E Glavina Del Rio T Tice H Copeland A Cheng JF Lucas S Chen F Bruce D Goodwin L Pitluck S Ivanova N Mavrommatis K Mikhailova N Pati A Chen A Palaniappan K Göker M Spring S Land M Hauser L Chang YJ Jeffries CC Chain P Bristow J Eisen JA Markowitz V Hugenholtz P Kyrpides NC Klenk HP Lapidus A 《Standards in genomic sciences》2009,1(1):38-45
Acidimicrobium ferrooxidans (Clark and Norris 1996) is the sole and type species of the genus, which until recently was the only genus within the actinobacterial family Acidimicrobiaceae and in the order Acidomicrobiales. Rapid oxidation of iron pyrite during autotrophic growth in the absence of an enhanced CO(2) concentration is characteristic for A. ferrooxidans. Here we describe the features of this organism, together with the complete genome sequence, and annotation. This is the first complete genome sequence of the order Acidomicrobiales, and the 2,158,157 bp long single replicon genome with its 2038 protein coding and 54 RNA genes is part of the Genomic Encyclopedia of Bacteria and Archaea project. 相似文献
219.
Land M Pukall R Abt B Göker M Rohde M Glavina Del Rio T Tice H Copeland A Cheng JF Lucas S Chen F Nolan M Bruce D Goodwin L Pitluck S Ivanova N Mavromatis K Ovchinnikova G Pati A Chen A Palaniappan K Hauser L Chang YJ Jefferies CC Saunders E Brettin T Detter JC Han C Chain P Bristow J Eisen JA Markowitz V Hugenholtz P Kyrpides NC Klenk HP Lapidus A 《Standards in genomic sciences》2009,1(1):21-28
Beutenbergia cavernae (Groth et al. 1999) is the type species of the genus and is of phylogenetic interest because of its isolated location in the actinobacterial suborder Micrococcineae. B. cavernae HKI 0122(T) is a Gram-positive, non-motile, non-spore-forming bacterium isolated from a cave in Guangxi (China). B. cavernae grows best under aerobic conditions and shows a rod-coccus growth cycle. Its cell wall peptidoglycan contains the diagnostic L-lysine ← L-glutamate interpeptide bridge. Here we describe the features of this organism, together with the complete genome sequence, and annotation. This is the first completed genome sequence from the poorly populated micrococcineal family Beutenbergiaceae, and this 4,669,183 bp long single replicon genome with its 4225 protein-coding and 53 RNA genes is part of the Genomic Encyclopedia of Bacteria and Archaea project. 相似文献
220.
Ivanova N Gronow S Lapidus A Copeland A Glavina Del Rio T Nolan M Lucas S Chen F Tice H Cheng JF Saunders E Bruce D Goodwin L Brettin T Detter JC Han C Pitluck S Mikhailova N Pati A Mavrommatis K Chen A Palaniappan K Land M Hauser L Chang YJ Jeffries CD Chain P Rohde C Göker M Bristow J Eisen JA Markowitz V Hugenholtz P Kyrpides NC Klenk HP 《Standards in genomic sciences》2009,1(2):126-132
Leptotrichia buccalis (Robin 1853) Trevisan 1879 is the type species of the genus, and is of phylogenetic interest because of its isolated location in the sparsely populated and neither taxonomically nor genomically adequately accessed family 'Leptotrichiaceae' within the phylum 'Fusobacteria'. Species of Leptotrichia are large, fusiform, non-motile, non-sporulating rods, which often populate the human oral flora. L. buccalis is anaerobic to aerotolerant, and saccharolytic. Here we describe the features of this organism, together with the complete genome sequence and annotation. This is the first complete genome sequence of the order 'Fusobacteriales' and no more than the second sequence from the phylum 'Fusobacteria'. The 2,465,610 bp long single replicon genome with its 2306 protein-coding and 61 RNA genes is a part of the Genomic Encyclopedia of Bacteria and Archaea project. 相似文献