Kooperativer Bibliotheksverbund

Berlin Brandenburg

and
and

Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
Filter
Type of Medium
Language
Year
  • 1
    Language: English
    In: Methods in enzymology, 2014, Vol.535, pp.225-47
    Description: The classical view that endocytosis serves only for growth factor receptor degradation and signaling termination has recently been challenged by an increasing number of reports showing that various growth factor receptors such as epidermal growth factor receptor (EGFR) continue to activate downstream signaling molecules en route to lysosomes prior to their degradation. Moreover, the trafficking route that the ligand-receptor complexes follow to enter the cell is mutually interconnected with the final signaling output. Endosomal resident effector proteins are compartmentalized and regulate the signaling and trafficking of the ligand-bound receptor complexes. Smad anchor for receptor activation (SARA) is an early endosomal protein facilitating TGF-β signaling cascade. Even though SARA was identified as an adaptor protein that regulates SMAD2 activation and TGF-β signal propagation, an increasing number of reports in various systems describe SARA as a trafficking regulator. Recently, SARA has been shown to interact with the E3 ubiquitin ligase RNF11 (RING finger protein 11) and members of the ESCRT-0 (endosomal sorting complex required for transport) complex functionally participating in the degradation of EGFR.
    Keywords: Egfr ; Immunoprecipitation ; Pull Down ; Rnf11 ; Sara ; Signal Transduction ; Carrier Proteins -- Metabolism ; Erbb Receptors -- Physiology ; Intracellular Signaling Peptides and Proteins -- Metabolism ; Serine Endopeptidases -- Metabolism
    ISBN: 9780123979254
    ISSN: 00766879
    E-ISSN: 1557-7988
    Source: MEDLINE/PubMed (U.S. National Library of Medicine)
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 2
    In: Nature Medicine, 2016
    Description: The efficacy of angiogenesis inhibitors in cancer is limited by resistance mechanisms that are poorly understood. Notably, instead of through the induction of angiogenesis, tumor vascularization can occur through the nonangiogenic mechanism of vessel co-option. Here we show that vessel co-option is associated with a poor response to the anti-angiogenic agent bevacizumab in patients with colorectal cancer liver metastases. Moreover, we find that vessel co-option is also prevalent in human breast cancer liver metastases, a setting in which results with anti-angiogenic therapy have been disappointing. In preclinical mechanistic studies, we found that cancer cell motility mediated by the actin-related protein 2/3 complex (Arp2/3) is required for vessel co-option in liver metastases in vivo and that, in this setting, combined inhibition of angiogenesis and vessel co-option is more effective than the inhibition of angiogenesis alone. Vessel co-option is therefore a clinically relevant mechanism of resistance to anti-angiogenic therapy and combined inhibition of angiogenesis and vessel co-option might be a warranted therapeutic strategy.
    Keywords: Liver Cancer -- Drug Therapy ; Cancer Metastasis -- Drug Therapy ; Angiogenesis Inhibitors -- Patient Outcomes;
    ISBN: 0003873023000
    ISSN: 1078-8956
    E-ISSN: 1546-170X
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 3
    Language: English
    In: Current Biology, 21 March 2016, Vol.26(6), pp.755-765
    Description: Expression of the initiator methionine tRNA (tRNA ) is deregulated in cancer. Despite this fact, it is not currently known how tRNA expression levels influence tumor progression. We have found that tRNA expression is increased in carcinoma-associated fibroblasts, implicating deregulated expression of tRNA in the tumor stroma as a possible contributor to tumor progression. To investigate how elevated stromal tRNA contributes to tumor progression, we generated a mouse expressing additional copies of the tRNA gene (2+tRNA mouse). Growth and vascularization of subcutaneous tumor allografts was enhanced in 2+tRNA mice compared with wild-type littermate controls. Extracellular matrix (ECM) deposited by fibroblasts from 2+tRNA mice supported enhanced endothelial cell and fibroblast migration. SILAC mass spectrometry indicated that elevated expression of tRNA significantly increased synthesis and secretion of certain types of collagen, in particular type II collagen. Suppression of type II collagen opposed the ability of tRNA -overexpressing fibroblasts to deposit pro-migratory ECM. We used the prolyl hydroxylase inhibitor ethyl-3,4-dihydroxybenzoate (DHB) to determine whether collagen synthesis contributes to the tRNA -driven pro-tumorigenic stroma in vivo. DHB had no effect on the growth of syngeneic allografts in wild-type mice but opposed the ability of 2+tRNA mice to support increased angiogenesis and tumor growth. Finally, collagen II expression predicts poor prognosis in high-grade serous ovarian carcinoma. Taken together, these data indicate that increased tRNA levels contribute to tumor progression by enhancing the ability of stromal fibroblasts to synthesize and secrete a type II collagen-rich ECM that supports endothelial cell migration and angiogenesis. Clarke et al. show that levels of the initiator tRNA are increased in carcinoma-associated fibroblasts. Using a transgenic approach to recapitulate this in vivo and quantitative mass spectrometry to characterize the stromal secretome, they show that elevated tRNA drives production of a type II collagen-rich ECM to drive tumor progression.
    Keywords: Initiator Methionine Trna (Trnaimet) ; Extracellular Matrix ; Tumor Angiogenesis ; Secretome ; Trna Repertoire ; Cell Migration ; Tumor Stroma ; Biology
    ISSN: 0960-9822
    E-ISSN: 1879-0445
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 4
    Language: English
    In: Journal of cell science, 01 October 2011, Vol.124(Pt 19), pp.3209-22
    Description: SARA, an early endosomal protein, plays a key role in TGFβ signalling, as it presents SMAD2 and SMAD3 for phosphorylation by the activated TGFβ receptors. Here, we show that ERBIN is a new SARA-interacting protein that can be recruited by SARA to early endosomes. ERBIN was recently shown to bind and segregate phosphorylated SMAD2 and SMAD3 (SMAD2/3) in the cytoplasm, thereby inhibiting SMAD2/3-dependent transcription. SARA binds to ERBIN using a new domain, which we have called the ERBID (ERBIN-binding domain), whereas ERBIN binds to SARA using a domain (amino acids 1208-1265) that also interacts with SMAD2 and SMAD3, which we have called the SSID (SARA- and SMAD-interacting domain). We additionally show that SARA competes with SMAD2/3 for binding to ERBIN. In agreement, overexpression of SARA or the ERBID peptide reverses the inhibitory effect of ERBIN on SMAD2/3-dependent transcription. Taken together, these data suggest that the response of cells to TGFβ and activin A can be influenced by the relative concentrations of SARA, ERBIN and SMAD2/3.
    Keywords: Adaptor Proteins, Signal Transducing -- Metabolism ; Intracellular Signaling Peptides and Proteins -- Metabolism ; Serine Endopeptidases -- Metabolism ; Smad2 Protein -- Metabolism ; Smad3 Protein -- Metabolism
    ISSN: 00219533
    E-ISSN: 1477-9137
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 5
    Language: English
    In: Methods in Enzymology, pp.225-247
    Description: The classical view that endocytosis serves only for growth factor receptor degradation and signaling termination has recently been challenged by an increasing number of reports showing that various growth factor receptors such as epidermal growth factor receptor (EGFR) continue to activate downstream signaling molecules en route to lysosomes prior to their degradation. Moreover, the trafficking route that the ligand–receptor complexes follow to enter the cell is mutually interconnected with the final signaling output. Endosomal resident effector proteins are compartmentalized and regulate the signaling and trafficking of the ligand-bound receptor complexes. Smad anchor for receptor activation (SARA) is an early endosomal protein facilitating TGF-β signaling cascade. Even though SARA was identified as an adaptor protein that regulates SMAD2 activation and TGF-β signal propagation, an increasing number of reports in various systems describe SARA as a trafficking regulator. Recently, SARA has been shown to interact with the E3 ubiquitin ligase RNF11 (RING finger protein 11) and members of the ESCRT-0 (endosomal sorting complex required for transport) complex functionally participating in the degradation of EGFR.
    Keywords: RNF11 ; SARA ; Immunoprecipitation ; Pull down ; EGFR
    ISBN: 978-0-12-397925-4
    ISSN: 0076-6879
    Source: ScienceDirect (Elsevier B.V.)
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 6
    Language: English
    In: ACS chemical biology, 19 December 2014, Vol.9(12), pp.2737-41
    Description: Bcl-2 family proteins are important regulators of apoptosis and its antiapoptotic members, which are overexpressed in many types of cancer, are of high prognostic significance, establishing them as attractive therapeutic targets. Quercetin, a natural flavonoid, has drawn much attention because it exerts anticancer effects, while sparing normal cells. A multidisciplinary approach has been employed herein, in an effort to reveal its mode of action including dose-response antiproliferative activity and induced apoptosis effect, biochemical and physicochemical assays, and computational calculations. It may be concluded that, quercetin binds directly to the BH3 domain of Bcl-2 and Bcl-xL proteins, thereby inhibiting their activity and promoting cancer cell apoptosis.
    Keywords: Gene Expression Regulation, Neoplastic ; Antineoplastic Agents, Phytogenic -- Chemistry ; Proto-Oncogene Proteins C-Bcl-2 -- Chemistry ; Quercetin -- Chemistry ; Bcl-X Protein -- Chemistry
    ISSN: 15548929
    E-ISSN: 1554-8937
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 7
    Language: English
    In: Cell Reports, 05 June 2018, Vol.23(10), pp.3042-3055
    Description: Primary cilia are microtubule-based organelles that detect mechanical and chemical stimuli. Although cilia house a number of oncogenic molecules (including Smoothened, KRAS, EGFR, and PDGFR), their precise role in cancer remains unclear. We have interrogated the role of cilia in acquired and resistance to a variety of kinase inhibitors, and found that, in several examples, resistant cells are distinctly characterized by an increase in the number and/or length of cilia with altered structural features. Changes in ciliation seem to be linked to differences in the molecular composition of cilia and result in enhanced Hedgehog pathway activation. Notably, manipulating cilia length via Kif7 knockdown is sufficient to confer drug resistance in drug-sensitive cells. Conversely, targeting of cilia length or integrity through genetic and pharmacological approaches overcomes kinase inhibitor resistance. Our work establishes a role for ciliogenesis and cilia length in promoting cancer drug resistance and has significant translational implications. Jenks et al. demonstrate that enhanced ciliogenesis can facilitate resistance to a number of kinase inhibitors. Both acquired and resistant cells show increases in cilia numbers and length and increased Hedgehog signaling. Targeting ciliogenesis or ciliary signaling overcomes kinase inhibitor resistance.
    Keywords: Cilia ; Kinase Inhibitor ; Resistance ; Hedgehog Pathway ; Fgfr ; Biology
    ISSN: 2211-1247
    E-ISSN: 2211-1247
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 8
    Language: English
    Description: The classical view that endocytosis serves only for growth factor receptor degradation and signaling termination has recently been challenged by an increasing number of reports showing that various growth factor receptors such as epidermal growth factor receptor (EGFR) continue to activate downstream signaling molecules en route to lysosomes prior to their degradation. Moreover, the trafficking route that the ligand–receptor complexes follow to enter the cell is mutually interconnected with the final signaling output. Endosomal resident effector proteins are compartmentalized and regulate the signaling and trafficking of the ligand-bound receptor complexes. Smad anchor for receptor activation (SARA) is an early endosomal protein facilitating TGF-β signaling cascade. Even though SARA was identified as an adaptor protein that regulates SMAD2 activation and TGF-β signal propagation, an increasing number of reports in various systems describe SARA as a trafficking regulator. Recently, SARA has been shown to interact with the E3 ubiquitin ligase RNF11 (RING finger protein 11) and members of the ESCRT-0 (endosomal sorting complex required for transport) complex functionally participating in the degradation of EGFR.
    Keywords: Rnf11 ; Sara ; Immunoprecipitation ; Pull Down ; Egfr ; Biology ; Anatomy & Physiology
    ISBN: 9780123979254
    ISBN: 0123979250
    Source: ScienceDirect Journals (Elsevier)
    Source: ScienceDirect Books (Elsevier)
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 9
    Description: Primary cilia are microtubule-based organelles that detect mechanical and chemical stimuli. Although cilia house a number of oncogenic molecules (including Smoothened, KRAS, EGFR, and PDGFR), their precise role in cancer remains unclear. We have interrogated the role of cilia in acquired and de novo resistance to a variety of kinase inhibitors, and found that, in several examples, resistant cells are distinctly characterized by an increase in the number and/or length of cilia with altered structural features. Changes in ciliation seem to be linked to differences in the molecular composition of cilia and result in enhanced Hedgehog pathway activation. Notably, manipulating cilia length via Kif7 knockdown is sufficient to confer drug resistance in drug-sensitive cells. Conversely, targeting of cilia length or integrity through genetic and pharmacological approaches overcomes kinase inhibitor resistance. Our work establishes a role for ciliogenesis and cilia length in promoting cancer drug resistance and has significant translational implications....
    Keywords: Fgfr ; Hedgehog Pathway ; Cilia ; Kinase Inhibitor ; Resistance
    ISSN: 2211-1247
    Source: DataCite
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 10
    Language: English
    Description: Primary cilia are microtubule-based organelles that detect mechanical and chemical stimuli. Although cilia house a number of oncogenic molecules (including Smoothened, KRAS, EGFR, and PDGFR), their precise role in cancer remains unclear. We have interrogated the role of cilia in acquired and de novo resistance to a variety of kinase inhibitors, and found that, in several examples, resistant cells are distinctly characterized by an increase in the number and/or length of cilia with altered structural features. Changes in ciliation seem to be linked to differences in the molecular composition of cilia and result in enhanced Hedgehog pathway activation. Notably, manipulating cilia length via Kif7 knockdown is sufficient to confer drug resistance in drug-sensitive cells. Conversely, targeting of cilia length or integrity through genetic and pharmacological approaches overcomes kinase inhibitor resistance. Our work establishes a role for ciliogenesis and cilia length in promoting cancer drug resistance and has significant translational implications.
    Description: This research was partly funded by the Institute of Cancer Research and by grants from Sarcoma UK (to B.E.T. [14.2014] and P.H.H. [3.2014]), Kent Cancer Trust (to M.M.), Hilfe fuer Krebskranke Kinder Frankfurt e.V. and Frankfurter Stiftung fuer Krebskranke Kinder (to J.C.), CRUK-CI Core Grant (C14303/A17197), and S.H.D. Fellowship (Wellcome Trust/Royal Society [107609]) (to M.D.R.). B.E.T. was supported by an ICR fellowship.
    Keywords: Fgfr ; Hedgehog Pathway ; Cilia ; Kinase Inhibitor ; Resistance
    Source: DSpace@Cambridge
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
Close ⊗
This website uses cookies and the analysis tool Matomo. Further information can be found on the KOBV privacy pages