- Title
- INPP4B is an oncogenic regulator in human colon cancer
- Creator
- Guo, S. T.; Chi, M. N.; Yan, X. G.; Farrelly, M.; Wang, F. H.; Lai, F.; Wang, J. F.; Li, Y. P.; Ackland, S.; Scott, R.; Agoulnik, I. U.; Hondermarck, H.; Yang, R. H.; Thorne, R. F.; Liu, T.; Zhang, X. D.; Jiang, C. C.; Guo, X. Y.; Zan, L. K.; Wang, C. Y.; Xi, Y. F.; Jin, L.; Croft, A.; Tseng, H.-Y.
- Relation
- NHMRC.1026458 http://purl.org/au-research/grants/nhmrc/1026458
- Relation
- Oncogene Vol. 35, Issue 23, p. 3049-3061
- Publisher Link
- http://dx.doi.org/10.1038/onc.2015.361
- Publisher
- Nature Publishing Group
- Resource Type
- journal article
- Date
- 2016
- Description
- Inositol polyphosphate 4-phosphatase type II (INPP4B) negatively regulates phosphatidylinositol 3-kinase signaling and is a tumor suppressor in some types of cancers. However, we have found that it is frequently upregulated in human colon cancer cells. Here we show that silencing of INPP4B blocks activation of Akt and serum-and glucocorticoid-regulated kinase 3 (SGK3), inhibits colon cancer cell proliferation and retards colon cancer xenograft growth. Conversely, overexpression of INPP4B increases proliferation and triggers anchorage-independent growth of normal colon epithelial cells. Moreover, we demonstrate that the effect of INPP4B on Akt and SGK3 is associated with inactivation of phosphate and tensin homolog through its protein phosphatase activity and that the increase in INPP4B is due to Ets-1-mediated transcriptional upregulation in colon cancer cells. Collectively, these results suggest that INPP4B may function as an oncogenic driver in colon cancer, with potential implications for targeting INPP4B as a novel approach to treat this disease.
- Subject
- bowel cancer; colorectal cancer; INPP4B
- Identifier
- http://hdl.handle.net/1959.13/1343604
- Identifier
- uon:29220
- Identifier
- ISSN:0950-9232
- Rights
- This work is licensed under a Creative Commons AttributionNonCommercial-NoDerivs 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http:// creativecommons.org/licenses/by-nc-nd/4.0/
- Language
- eng
- Full Text
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