Silencing of Jagged1 inhibits cell growth and invasion in colorectal cancer

Dai, Y., Wilson, G., Huang, B., Peng, M., Teng, G., Zhang, D., Zhang, R., Ebert, M. P. A., Chen, J., Wong, B. C. Y., Chan, K. W., George, J. and Qiao, L. (2014) Silencing of Jagged1 inhibits cell growth and invasion in colorectal cancer. Cell Death and Disease, 5 4: e1170.1-e1170.9. doi:10.1038/cddis.2014.137

Author Dai, Y.
Wilson, G.
Huang, B.
Peng, M.
Teng, G.
Zhang, D.
Zhang, R.
Ebert, M. P. A.
Chen, J.
Wong, B. C. Y.
Chan, K. W.
George, J.
Qiao, L.
Title Silencing of Jagged1 inhibits cell growth and invasion in colorectal cancer
Journal name Cell Death and Disease   Check publisher's open access policy
ISSN 2041-4889
Publication date 2014-04-01
Sub-type Article (original research)
DOI 10.1038/cddis.2014.137
Open Access Status DOI
Volume 5
Issue 4
Start page e1170.1
End page e1170.9
Total pages 9
Place of publication London, United Kingdom
Publisher Nature Publishing
Language eng
Formatted abstract
Dysregulated Notch signaling has a critical role in the tumorigenesis. Jagged1, a Notch ligand, is overexpressed in various human cancers. Recent studies revealed the involvement of Jagged1 in colorectal cancer (CRC) development. These basic studies provide a promising potential for inhibition of the Notch pathway for the treatment of CRC. Herein, we aimed to investigate the consequences of targeting Jagged1 using shRNA on CRC both in vitro and in vivo to test their potential to inhibit this key element for CRC treatment. We found that downregulation of Jagged1 with lentiviral Jagged1-shRNA resulted in decreased colon cancer cell viability in vitro, most likely mediated through reduced cell proliferation. Importantly, Jagged1 knockdown induced G0/G1 phase cell cycle arrest, with reduced Cyclin D1, Cyclin E and c-Myc expression. Silencing of Jagged1 reduced the migration and invasive capacity of the colon cancer cells in vitro. Furthermore, colon cancer cells with knockdown of Jagged1 had much slower growth rate than control cells in a xenograft mouse model in vivo, with a marked downregulation of cell proliferation markers (PCNA, Ki-67, and c-Myc) and metastasis markers (MMP-2 and MMP-9). These findings rationalize a mechanistic approach to CRC treatment based on Jagged1-targeted therapeutic development.

Keyword Colorectal cancer
Notch signaling
Xenograft tumors
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2015 Collection
School of Biomedical Sciences Publications
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