Cytokeratin 8 associates with the external leaflet of plasma membranes in tumour cells

Gires, Olivier; Andratschke, Michaela; Schmitt, Bärbel; Mack, Brigitte; Schaffrik, Martina

doi:10.1016/j.bbrc.2005.01.074

Cited by 28 publications

(25 citation statements)

References 22 publications

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“…CK7 and CK8 are simple-epithelial ductal-type CKs that are widely distributed and often coexpressed. Little is known about CK7, which usually pairs with CK19, but the related CK8, which pairs with CK18, has been shown to associate with the external leaflet of the PM in cancer cells (Gires et al, 2005). In addition, CKs are necessary for membrane incorporation of glucose transporters 1 and 3 (Vijayaraj et al, 2009).…”

mentioning

confidence: 99%

G Protein-Coupled Estrogen Receptor 1/G Protein-Coupled Receptor 30 Localizes in the Plasma Membrane and Traffics Intracellularly on Cytokeratin Intermediate Filaments

Sandén¹,

Broselid

Cornmark³

et al. 2010

Mol Pharmacol

109

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mentioning

confidence: 99%

G Protein-Coupled Estrogen Receptor 1/G Protein-Coupled Receptor 30 Localizes in the Plasma Membrane and Traffics Intracellularly on Cytokeratin Intermediate Filaments

Sandén¹,

Broselid

Cornmark³

et al. 2010

Mol Pharmacol

109

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“…Our experiments suggest that CK8 has a surface-exposed component in colon adenocarcinoma cells that allows its interaction with intestinal pathogens. This theory is supported by several reports on CK8/CK18 membrane localization in colon tumor cells (10,13,17,20,24). Furthermore, Pankov et al found that this surface localization was present only in tumor cells and not in healthy tissue (29).…”

Section: Discussionmentioning

confidence: 52%

“…Interestingly, cytokeratin-8 (CK8) and CK18 received the most significant emPAI values and peptide hits. Importantly, literature supports a role for CK8 as a potential bacterial adherence factor (17,20) but also indicates that it is expressed at increased levels by colon tumor cells (2), which could be relevant for the increased incidence of infection of S. gallolyticus in CRC patients (4a). For these reasons CK8 was selected as a target for further evaluation in this study.…”

Section: Resultsmentioning

confidence: 99%

Surface-Affinity Profiling To Identify Host-Pathogen Interactions

et al. 2011

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Proteolytic treatment of intact bacterial cells has proven to be a convenient approach for the identification of surface-exposed proteins. This class of proteins directly interacts with the outside world, for instance, during adherence to human epithelial cells. Here, we aimed to identify host receptor proteins by introducing a preincubation step in which bacterial cells were first allowed to capture human proteins from epithelial cell lysates. Using Streptococcus gallolyticus as a model bacterium, liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis of proteolytically released peptides yielded the identification of a selective number of human epithelial proteins that were retained by the bacterial surface. Of these potential receptors for bacterial interference, (cyto)keratin-8 (CK8) was verified as the most significant hit, and its surface localization was investigated by subcellular fractionation and confocal microscopy. Interestingly, bacterial enolase could be assigned as an interaction partner of CK8 by MS/MS analysis of cross-linked protein complexes and complementary immunoblotting experiments. As surface-exposed enolase has a proposed role in epithelial adherence of several Gram-positive pathogens, its interaction with CK8 seems to point toward a more general virulence mechanism. In conclusion, our study shows that surface-affinity profiling is a valuable tool to identify novel adhesin-receptor pairs, which advocates its application in other hybrid biological systems.The key to bacterial infection of host tissue is the establishment of a dependable connection between the bacterium and host surface structures. This is essential for the bacteria to withstand mechanical cleansing processes and to compete with other bacterial strains for microbial succession (16). After initial adherence, several pathogens can invade host cells using intracellular structures, e.g., the cytoskeleton, to sustain growth and prolong their survival times (8, 12). Ultimately, both adhesion and internalization of pathogenic bacteria will directly or indirectly (via induction of host responses) cause damage to the infected tissue. It is therefore important to fully understand the mechanisms underlying pathogenic interference so that new methods to prevent pathogenic bacteria from initiating an infectious process can be developed. In addition, knowledge about pathogen-specific interactions and subsequent responses may aid in the diagnosis of corresponding diseases.Current advances in proteomic technologies provide opportunities to compare the protein content from different biologic systems, making it possible to characterize host-pathogen interactions in a global view. Therefore, the aim of this study was to explore the use of a proteolytic shaving approach coupled to liquid chromatography-tandem mass spectrometry (LC-MS/ MS) to identify potential host proteins for bacterial interference. For this purpose, intact bacterial cells were first allowed to selectively bind host proteins from epithelial cell lysates, after wh...

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“…In addition, there are numerous evidence for abnormalities of K8/K18 expression in CRC (48)(49)(50)(51)(52). Despite K8 and K18 being traditionally described as cytoskeletal proteins, several studies have reported the presence of both keratins on the cell membrane in breast carcinoma (53), K18 in healthy and tumor hepatocytes (54) and K8 in CRC cells but not in their healthy counterparts (55). Therefore, K8 and K18 might have a cell membrane-associated glucide, such as the CDw75 epitope.…”

Section: Discussionmentioning

confidence: 99%

Identification of proteins with the CDw75 epitope in human colorectal cancer

2017

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Abstract. The CDw75 epitope is an α(2,6) sialylated antigen overexpressed in colorectal cancer (CRC), where its expression correlates with the progression of the disease. The CDw75 epitope is located mainly in N-glycoproteins, whose identity remains unknown. The aim of the present study was to identify proteins with the CDw75 epitope as a strategy to deepen the understanding of molecular pathogenesis of CRC and to identify novel biomarkers for this disease. For this purpose, a two-dimensional electrophoresis approach was employed. Protein spots in the gels were matched to the corresponding CDw75 positive spots in the immunoblotted polyvinylidene difluoride membranes, and further identification of the protein species was performed by mass spectrometry. Additionally, one-dimensional western blotting experiments were performed to verify the expression of these candidate proteins in the colorectal tissue and their coincidence in molecular mass with the CDw75-positive bands. The findings of the present study indicate that haptoglobin and the keratins 8 (K8) and 18 (K18) are proteins with the CDw75 epitope in the colorectal tissue from CRC patients and also suggest novel functions and cellular locations for these proteins in the colorectal tissue and in relation to CRC.

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Cytokeratin 8 associates with the external leaflet of plasma membranes in tumour cells

Cited by 28 publications

References 22 publications

G Protein-Coupled Estrogen Receptor 1/G Protein-Coupled Receptor 30 Localizes in the Plasma Membrane and Traffics Intracellularly on Cytokeratin Intermediate Filaments

G Protein-Coupled Estrogen Receptor 1/G Protein-Coupled Receptor 30 Localizes in the Plasma Membrane and Traffics Intracellularly on Cytokeratin Intermediate Filaments

Surface-Affinity Profiling To Identify Host-Pathogen Interactions

Identification of proteins with the CDw75 epitope in human colorectal cancer

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