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Collagen I Promotes Metastasis in Pancreatic Cancer by Activating c-Jun NH2-Terminal Kinase 1 and Up-regulating N-Cadherin Expression
Open accessAbstract
We have previously shown that N-cadherin expression is associated with tumor invasion, and that some cancer cells respond to specific extracellular matrix molecules by up-regulating N-cadherin. Pancreatic cancer is characterized by excessive deposition of type I collagen. Here, we show that human pancreatic cancer cells respond to collagen I, but not other matrices, by increasing motility and up-regulating mesenchymal markers, including N-cadherin. Both collagen I–mediated motility and metastasis in a mouse model for pancreatic cancer were inhibited by N-cadherin knockdown. Furthermore, inhibiting c-Jun NH2-terminal kinase (JNK) with chemical inhibitors or short hairpin RNA abrogated all collagen I–induced changes. We show that JNK1 is activated in response to collagen I, which increases tumorigenesis by up-regulating N-cadherin expression and by increasing motility. (Cancer Res 2006; 66(24): 11745-53)
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Cited by
Signaling mechanisms of the epithelial-mesenchymal transition
Gonzalez, D. M., & Medici, D. (2014) · Science Signaling · doi:10.1126/scisignal.2005189 · Cited by 1,721
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Hosein, A. N., Brekken, R. A., & Maitra, A. (2020) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-020-0300-1 · Cited by 950
KRAS, Hedgehog, Wnt and the twisted developmental biology of pancreatic ductal adenocarcinoma
Morris, J. P., Wang, S. C., & Hebrok, M. (2010) · Nature Reviews Cancer · doi:10.1038/nrc2899 · Cited by 567
Sengupta, S., den Boon, J. A., Chen, I.-H., Newton, M. A., Stanhope, S. A., Cheng, Y.-J., Chen, C.-J., Hildesheim, A., Sugden, B., & Ahlquist, P. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0801130105 · Cited by 398
Microenvironmental Determinants of Pancreatic Cancer
Hessmann, E., Buchholz, S. M., Demir, I. E., Singh, S. K., Gress, T. M., Ellenrieder, V., & Neesse, A. (2020) · Physiological Reviews · doi:10.1152/physrev.00042.2019 · Cited by 331
Metadata
- Authors
- Shintani, Y., Hollingsworth, M. A., Wheelock, M. J., & Johnson, K. R.
- Venue
- Cancer Research
- Published
- 2006-12-15
- Volume
- 66
- Issue
- 24
- Pages
- 11745-11753
- ISSN
- 0008-5472 (ISSN-L)
- 1538-7445
- OpenAlex
- W2159986837
- Cited by
- 221
- References
- 0
- FWCI
- 3.41
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Shintani, Y., Hollingsworth, M. A., Wheelock, M. J., & Johnson, K. R. (2006). Collagen I Promotes Metastasis in Pancreatic Cancer by Activating c-Jun NH2-Terminal Kinase 1 and Up-regulating N-Cadherin Expression. Cancer Research. https://doi.org/10.1158/0008-5472.can-06-2322
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