The DOI matches its Crossref record; 40 of the 40 references it cites were found in a registry or an index.
MUC1 enhances invasiveness of pancreatic cancer cells by inducing epithelial to mesenchymal transition
Open accessAbstract
Increased motility and invasiveness of pancreatic cancer cells are associated with epithelial to mesenchymal transition (EMT). Snai1 and Slug are zinc-finger transcription factors that trigger this process by repressing E-cadherin and enhancing vimentin and N-cadherin protein expression. However, the mechanisms that regulate this activation in pancreatic tumors remain elusive. MUC1, a transmembrane mucin glycoprotein, is associated with the most invasive forms of pancreatic ductal adenocarcinomas (PDA). In this study, we show that over expression of MUC1 in pancreatic cancer cells triggers the molecular process of EMT, which translates to increased invasiveness and metastasis. EMT was significantly reduced when MUC1 was genetically deleted in a mouse model of PDA or when all seven tyrosines in the cytoplasmic tail of MUC1 were mutated to phenylalanine (mutated MUC1 CT). Using proteomics, RT–PCR and western blotting, we revealed a significant increase in vimentin, Slug and Snail expression with repression of E-Cadherin in MUC1-expressing cells compared with cells expressing the mutated MUC1 CT. In the cells that carried the mutated MUC1 CT, MUC1 failed to co-immunoprecipitate with β-catenin and translocate to the nucleus, thereby blocking transcription of the genes associated with EMT and metastasis. Thus, functional tyrosines are critical in stimulating the interactions between MUC1 and β-catenin and their nuclear translocation to initiate the process of EMT. This study signifies the oncogenic role of MUC1 CT and is the first to identify a direct role of the MUC1 in initiating EMT during pancreatic cancer. The data may have implications in future design of MUC1-targeted therapies for pancreatic cancer.
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Cites
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Cited by
Zhu, Y., Knolhoff, B. L., Meyer, M. A., Nywening, T. M., West, B. L., Luo, J., Wang-Gillam, A., Goedegebuure, S. P., Linehan, D. C., & DeNardo, D. G. (2014) · Cancer Research · doi:10.1158/0008-5472.can-13-3723 · Cited by 1,324
Mechanisms of cancer dissemination along nerves
Amit, M., Na'ara, S., & Gil, Z. (2016) · Nature Reviews Cancer · doi:10.1038/nrc.2016.38 · Cited by 308
Cellular and Molecular Biology of Airway Mucins
(2013) · International Review of Cell and Molecular Biology · doi:10.1016/b978-0-12-407697-6.00004-0 · Cited by 189
Dhanisha, S. S., Guruvayoorappan, C., Drishya, S., & Abeesh, P. (2018) · Critical Reviews in Oncology/Hematology · doi:10.1016/j.critrevonc.2017.12.006 · Cited by 194
Norris, A. M., Gore, A., Balboni, A., Young, A., Longnecker, D. S., & Korc, M. (2013) · Oncogene · doi:10.1038/onc.2012.394 · Cited by 79
Metadata
- Authors
- Roy, L. D., Sahraei, M., Subramani, D. B., Besmer, D., Nath, S., Tinder, T. L., Bajaj, E., Shanmugam, K., Lee, Y. Y., Hwang, S. I. L., Gendler, S. J., & Mukherjee, P.
- Venue
- Oncogene
- Published
- 2010-11-22
- Volume
- 30
- Issue
- 12
- Pages
- 1449-1459
- ISSN
- 0950-9232 (ISSN-L)
- 1476-5594
- OpenAlex
- W2095887087
- Cited by
- 263
- References
- 40
- FWCI
- 8.98
- Type
- journal article
- Language
- en
- Open access
- green
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- Roy, L. D., Sahraei, M., Subramani, D. B., Besmer, D., Nath, S., Tinder, T. L., Bajaj, E., Shanmugam, K., Lee, Y. Y., Hwang, S. I. L., Gendler, S. J., & Mukherjee, P. (2011). MUC1 enhances invasiveness of pancreatic cancer cells by inducing epithelial to mesenchymal transition. Oncogene. https://doi.org/10.1038/onc.2010.526
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