Please use this identifier to cite or link to this item:
https://doi.org/10.1158/0008-5472.CAN-10-1487
Title: | Phosphatase PRL-3 is a direct regulatory target of TGFb in colon cancer metastasis | Authors: | Jiang, Y Liu, X.-Q Rajput, A Geng, L Ongchin, M Zeng, Q Taylor, G.S Wang, J |
Keywords: | cancer growth factor cancer growth factor beta prl 3 protein protein tyrosine phosphatase Smad protein unclassified drug animal cell animal experiment animal model apoptosis article cancer survival cell survival colon cancer controlled study enzyme inhibition gene overexpression gene silencing metastasis mouse nonhuman priority journal protein expression signal transduction Animals Cell Line, Tumor Chromatin Immunoprecipitation Colonic Neoplasms Electrophoretic Mobility Shift Assay Gene Expression Regulation, Neoplastic Mice Neoplasm Proteins Phosphatidylinositol 3-Kinases Protein Tyrosine Phosphatases Proto-Oncogene Proteins c-akt Signal Transduction Smad Proteins Transforming Growth Factor beta |
Issue Date: | 2011 | Citation: | Jiang, Y, Liu, X.-Q, Rajput, A, Geng, L, Ongchin, M, Zeng, Q, Taylor, G.S, Wang, J (2011). Phosphatase PRL-3 is a direct regulatory target of TGFb in colon cancer metastasis. Cancer Research 71 (1) : 234-244. ScholarBank@NUS Repository. https://doi.org/10.1158/0008-5472.CAN-10-1487 | Rights: | Attribution 4.0 International | Abstract: | Metastasis causes most deaths from cancer yet mechanistic understanding and therapeutic options remain limited. Overexpression of the phosphatase PRL-3 (phosphatase of regenerating liver) is associated with metastasis of colon cancer. Here, we show that PRL-3 is a direct target of signaling by TGFb, which is broadly implicated in progression and metastasis. We found that suppression of PRL-3 expression by TGFb was mediated by Smad-dependent inhibition of PRL-3 transcription at the level of promoter activity. PRL-3 activation stimulated PI3K/AKT signaling that caused resistance to stress-induced apoptosis. PRL-3 overexpression promoted metastatic colonization in an orthotopic mouse model of colon cancer, whereas PRL-3 knockdown reduced metastatic potential. Altered metastatic phenotypes were not derivative of primary tumor development or local invasion but could be attributed to PRL-3-mediated cell survival. Our findings suggest that inhibiting PRL-3 expression might be an important mechanism through which TGFb suppresses metastasis in colon cancer. In addition, our findings suggest that loss of TGFb signaling, which occurs commonly during colon cancer progression, is sufficient to activate a PRL-3-mediated cell survival pathway that can selectively promote metastasis. Therefore, a major implication of our findings is that PRL-3 antagonists may offer significant value for antimetastatic therapy in patients with colon cancer. ©2010 AACR. | Source Title: | Cancer Research | URI: | https://scholarbank.nus.edu.sg/handle/10635/180976 | ISSN: | 0008-5472 | DOI: | 10.1158/0008-5472.CAN-10-1487 | Rights: | Attribution 4.0 International |
Appears in Collections: | Staff Publications Elements |
Show full item record
Files in This Item:
File | Description | Size | Format | Access Settings | Version | |
---|---|---|---|---|---|---|
10_1158_0008-5472_CAN-10-1487.pdf | 1.09 MB | Adobe PDF | OPEN | None | View/Download |
This item is licensed under a Creative Commons License