MUC1 (episialin) expression in non-small cell lung cancer is independent of EGFR and c-erbB-2 expression and correlates with poor survival in node positive patients

Guddo, Francesca; Giatromanolaki, Alexandra; Koukourakis, M.; Reina, C.; Vignola, Antonio-Maurizio; Chlouverakis, Gregorios; Hilkens, John; Gatter, K C; Harris, Adrian L.; Bonsignore, G

doi:10.1136/jcp.51.9.667

Cited by 103 publications

(97 citation statements)

References 21 publications

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“…This polarized distribution of MUC1 is lost in many cancer cells (Guddo et al, 1998). Aberrantly glycosylated MUC1 has also been observed in adenocarcinomas.…”

Section: Discussionmentioning

confidence: 94%

Activation of ErbB3–PI3-kinase pathway is correlated with malignant phenotypes of adenocarcinomas

et al. 2003

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Signet-ring cell carcinomas are malignant dedifferentiated carcinomas, which are frequently found in the stomach. We previously demonstrated that a 200 kDa protein is often constitutively phosphorylated on tyrosine and bound to phosphatidylinositol 3-kinase (PI3-kinase) in signetring cell carcinoma cells. In this study, we purified the 200 kDa protein from an extract of NUGC-4 cells, a cell line of signet-ring cell carcinoma, and identified it as ErbB3. ErbB3 was found to be phosphorylated selectively in dedifferentiated adenocarcinoma cell lines among various gastric cancer cell lines. Expression of a constitutively active chimeric receptor consisting of ErbB2 and ErbB3 in HCC2998 cells, a highly differentiated adenocarcinoma cell line, revealed that the signaling triggered by phosphorylation of ErbB3 was important for dedifferentiated phenotypes such as loss of cell-cell interaction and high expression of MUC1/DF3 antigen, a marker of the malignant tumors. Taken together, activation of ErbB3 pathway may contribute to the development of dedifferentiated carcinomas.

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“…This polarized distribution of MUC1 is lost in many cancer cells (Guddo et al, 1998). Aberrantly glycosylated MUC1 has also been observed in adenocarcinomas.…”

Section: Discussionmentioning

confidence: 94%

Activation of ErbB3–PI3-kinase pathway is correlated with malignant phenotypes of adenocarcinomas

et al. 2003

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“…This mucin change occurs in company with disappearance of cilia ( Figure 1B), disassembly of AJs (Figure 2), and intracellular complex formation between MUC1-CT and ␤-catenin ( Figure 3C). Although intracellular translocation of MUC1-CT is frequently observed in various tumor cells, 39 the biological significance of its intracellular localization in complex with ␤-catenin in a nonmalignant model of the airway epithelium remains unclear. Accumulating evidence suggests that the cytoplasmic tail of MUC1 interacts with various growth factor receptors and ␤-catenin.…”

Section: Discussionmentioning

confidence: 99%

Cigarette Smoke Induces Epidermal Growth Factor Receptor-Dependent Redistribution of Apical MUC1 and Junctional β-Catenin in Polarized Human Airway Epithelial Cells

Chen

Gallup

Nikulina

et al. 2010

The American Journal of Pathology

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Cigarette smoke (CS) accounts for nearly 90% of lung cancer deaths worldwide; however, an incomplete understanding of how CS initiates preneoplastic changes in the normal airway hinders early diagnosis. Short-term exposure to CS causes aberrant activation of epidermal growth factor receptor (EGFR) and canonical Wnt/␤-catenin signaling pathways in human bronchial epithelial (HBE) cells. We hypothesize that this response is elicited through the disruption of spatially segregated cell membrane proteins in the polarized airway epithelium. Using an in vitro model of highly differentiated HBE cells, we observed membrane characteristics consistent with the native airway, including the presence of a membrane mucin, MUC1, at the apical cell pole, ␤-catenin at the apicallateral membrane, and EGFR at the basolateral membrane. Following exposure to smoke, intercellular spaces enlarge and cilia disappear. This histopathology is accompanied by molecular events that include perinuclear trafficking of basolateral EGFR, EGFR phosphorylation, pEGFR-mediated phosphorylation of MUC1's cytoplasmic tail (CT), loss of E-cadherin/␤-catenin complexes at the adherens junctions (AJs), intracellular formation and nuclear shuffling of ␤-catenin/MUC1-CT complexes, and, ultimately, upregulation and nuclear localization of Wnt nuclear effector, Lef-1. In the presence of EGFR inhibitor, AG1478, CS-induced histopathology and molecular events were inhibited. These data point to EGFR as a portal through which CS mediates its damaging effects on AJ-mediated cell polarity and activation of canonical Wnt/␤-catenin signaling.

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“…Overexpression of MUC1 in carcinoma cells (18) is expected to have an effect on cellular behavior similar to that of loss of function of the major epithelial adhesion molecule E-cadherin, which has been shown recently to promote invasion and metastasis of carcinoma cells (48). Overexpression of MUC1 in several cancers is reported to correlate with poor prognosis (16). MUC1 has been used as an antigen for detection of recurrence of breast cancer, and detection of MUC1 mRNA may be useful as a marker for metastasis of gastric cancer (2).…”

Section: Discussionmentioning

confidence: 99%

MUC1 Induced by Epstein-Barr Virus Latent Membrane Protein 1 Causes Dissociation of the Cell-Matrix Interaction and Cellular Invasiveness via STAT Signaling

Kondo

Yoshizaki

Wakisaka

et al. 2007

J Virol

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MUC1 (episialin) expression in non-small cell lung cancer is independent of EGFR and c-erbB-2 expression and correlates with poor survival in node positive patients

Cited by 103 publications

References 21 publications

Activation of ErbB3–PI3-kinase pathway is correlated with malignant phenotypes of adenocarcinomas

Activation of ErbB3–PI3-kinase pathway is correlated with malignant phenotypes of adenocarcinomas

Cigarette Smoke Induces Epidermal Growth Factor Receptor-Dependent Redistribution of Apical MUC1 and Junctional β-Catenin in Polarized Human Airway Epithelial Cells

MUC1 Induced by Epstein-Barr Virus Latent Membrane Protein 1 Causes Dissociation of the Cell-Matrix Interaction and Cellular Invasiveness via STAT Signaling

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