Keratin 8/18 breakdown and reorganization during apoptosis

Schütte, B.; Henfling, Mieke E.R.; Kölgen, Wendy; Bouman, Maartje; Meex, Steven J.R.; Leers, Mathie P.G.; Nap, Marius; Björklund, Viveka; Björklund, Peter; Björklund, Bertil; Lane, E. Birgitte; Omary, M. Bishr; Jörnvall, Hans; Ramaekers, Frans C. S.

doi:10.1016/j.yexcr.2004.02.019

Cited by 184 publications

(170 citation statements)

References 53 publications

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“…Presence of CK7 is reported in some studies (Moll, Franke et al 1982;Casanova, Bravo et al 1995;Wildi, Kleeff et al 1999;Zhou, Toivola et al 2003;Schutte, Henfling et al 2004;Toivola, Krishnan et al 2004;Moll, Divo et al 2008;Omary, Ku et al 2009;Habtezion, Toivola et al 2011) while there are also some reports stating the absence of this CK in the intestine (Ramaekers, Huysmans et al 1987;Oriolo, Wald et al 2007). Several type I cytokeratins are present in intestinal epithelial cells.…”

Section: Intestinal Cytokeratins -Model To Study Cytokeratin Changes mentioning

confidence: 92%

Cytokeratins of the Liver and Intestine Epithelial Cells During Development and Disease

Chougule¹,

Sumitran–Holgersson²

2012

Cytokeratins - Tools in Oncology

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Section: Intestinal Cytokeratins -Model To Study Cytokeratin Changes mentioning

confidence: 92%

Cytokeratins of the Liver and Intestine Epithelial Cells During Development and Disease

Chougule¹,

Sumitran–Holgersson²

2012

Cytokeratins - Tools in Oncology

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“…Caspase-cleaved cytokeratin 18 (cCK18) was evaluated using the M30 Apoptosense ELISA kit obtained from PEVIVA AB (Bromma, Sweden) (18). The cells (5x10 3 ) were seeded in a 96-well plate and cultured for 6, 24 or 48 h following the addition of 0.3 µM Gal-9.…”

Section: Methodsmentioning

confidence: 99%

Galectin-9: An anticancer molecule for gallbladder carcinoma

Tadokoro

Morishita

Fujihara

et al. 2016

International Journal of Oncology

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Abstract. Gallbladder cancer (GBC) is the most common and aggressive type of biliary tract cancer. There are various histological types of GBC, and the vast majority of GBC cases are adenocarcinomas. Squamous and adenosquamous carcinomas are rare GBC subtypes that are traditionally considered to be more aggressive and to be associated with a poorer prognosis than adenocarcinoma. Galectin-9 (Gal-9), a tandem-repeattype galectin, has been reported to induce apoptosis-mediated elimination of various cancers, including hepatocellular carcinoma, cholangiocarcinoma, and hematologic malignancies. Therefore, we investigated the antitumor effects of Gal-9 on GBC in vitro and in vivo. In our in vitro experiments, Gal-9 suppressed cell proliferation in various GBC cell lines but not in the OCUG-1 cell line, which represents a poorly differentiated type of adenosquamous carcinoma. Gal-9 induced the apoptosis of Gal-9-sensitive GBC cells by increasing the levels of caspase-cleaved keratin 18 and phosphorylated p53. However, Gal-9 did not affect the expression of various cell cycle-related proteins. In addition, Gal-9 suppressed tumor growth by implanted human GBC cells in a xenograft model. Furthermore, Gal-9 induced the phosphorylation of the Ephrin type-B receptor, and the microRNA (miRNA) expression profile was markedly altered by Gal-9. Based on these results, various miRNAs might contribute to the suppression of tumor growth. Our data reveal that Gal-9 suppresses the growth of GBC, possibly by inducing apoptosis and altering miRNA expression. Thus, Gal-9 might serve as a therapeutic agent for the treatment of GBC.

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“…Increasing evidence exists to suggest that cytokeratins have an important role during epithelial apoptosis. Degradation of type I cytokeratins (including CK18) by activated caspases 3, 7 and 9 with consequent loss of mechanical integrity of the cell occurs during the execution phase of apoptosis to facilitate cell shrinkage and formation of apoptotic bodies (Leers et al, 1999;Schutte et al, 2004). During this process, CK18 is cleaved at two specific sites along the non-helical linker region of the protein (Asp238 and Asp396) exposing the Asp396 neo-epitope with the subsequent release of cleaved cytokeratin fragments into the extracellular space.…”

Section: Histopathological Assessment Of Necrosis and Apoptosis In Rementioning

confidence: 99%

Considerations for the use of plasma cytokeratin 18 as a biomarker in pancreatic cancer

et al. 2010

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BACKGROUND: Enzyme-linked immunoassays of full-length (M65) and/or caspase-cleaved (M30) cytokeratin 18 (CK18) released from epithelial cells undergoing necrosis and/or apoptosis, respectively, may have prognostic or predictive biomarker utility in a range of solid tumour types. Characterisation of baseline levels of circulating full length and cleaved CK18 specifically in patients with pancreatic cancer. METHODS: Plasma samples from 103 patients with pancreatic cancer stored at À80 1C were assayed for M65 and M30 levels. The median (inter-quartile range (IQR)) duration of plasma storage was 34 (23 -57) months. Patients with metastatic disease (n ¼ 19) were found to have greater median (IQR) M65 levels (1145 (739 -1698) U l À1 ) compared with the locally advanced (n ¼ 20; 748 (406 -1150) U l À1 ) and resected (n ¼ 64; 612 (331 -987) U l À1 ) patients (P ¼ 0.002). Elevated M65 levels were associated with poorer overall survival on univariate (Po0.001) but not multivariate (P ¼ 0.202) analysis. M65 concentrations also exhibited significant associations with concurrent serum -bilirubin levels (Po0.001) and the duration of plasma storage (Po0.001). CONCLUSIONS: Baseline plasma CK18 levels in pancreatic cancer are affected by the presence of obstructive jaundice and prolonged plasma storage. Clinical biomarker studies utilising serial CK18 levels are warranted in pancreatic cancer, provided consideration is given to these potentially confounding factors. Pancreatic ductal adenocarcinoma is a leading cause of cancer deaths (http://www-dep.iarc.fr/) wherein, because of its characteristically late presentation, only 10 -15% of patients present with resectable tumours (Alexakis et al, 2004). For the remaining 85 -90% of patients presenting with inoperable disease, administration of systemic chemotherapy represents the most widely utilised palliative treatment modality (Yip et al, 2006). Conventional chemotherapy regimens incorporating either 5-FU or gemcitabine typically result in only modest improvement in overall survival (Sultana et al, 2007). One of the key challenges in accelerating improved cancer therapeutics is the identification of biomarkers to enable early objective assessment of tumour responses to chemotherapy (Kummar et al, 2007).Necrosis of malignant and normal epithelial cells cause release of cytokeratin 18 (CK18) (Kramer et al, 2004), a type I intermediate filament protein and a component of the intracellular cytoskeleton (Fuchs and Weber, 1994). Caspase-mediated cleavage of the CK18 contributes to the degradation of the intracellular cytoskeleton if epithelial cells undergo apoptosis (Leers et al, 1999). Enzymelinked immunosorbent assays (ELISAs) have been developed to measure circulating concentrations of both full-length CK18 (M65) and caspase-cleaved CK18 fragments (M30) (Kramer et al, 2004). Thus, the M65 ELISA reports necrotic and apoptotic epithelial cell death, whereas the M30 ELISA reports levels of epithelial apoptosis specifically (Kramer et al, 2004). Early studies suggest that these assays ...

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Keratin 8/18 breakdown and reorganization during apoptosis

Cited by 184 publications

References 53 publications

Cytokeratins of the Liver and Intestine Epithelial Cells During Development and Disease

Cytokeratins of the Liver and Intestine Epithelial Cells During Development and Disease

Galectin-9: An anticancer molecule for gallbladder carcinoma

Considerations for the use of plasma cytokeratin 18 as a biomarker in pancreatic cancer

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