Please use this identifier to cite or link to this item:
|Title:||Integration of regulatory networks by NKX3-1 promotes androgen-dependent prostate cancer survival|
Senali Abayratna Wansa, K.D.
|Citation:||Tan, P.Y., Chang, C.W., Chng, K.R., Senali Abayratna Wansa, K.D., Sung, W.-K., Cheung, E. (2012). Integration of regulatory networks by NKX3-1 promotes androgen-dependent prostate cancer survival. Molecular and Cellular Biology 32 (2) : 399-414. ScholarBank@NUS Repository. https://doi.org/10.1128/MCB.05958-11|
|Abstract:||The NKX3-1 gene is a homeobox gene required for prostate tumor progression, but how it functions is unclear. Here, using chromatin immunoprecipitation coupled to massively parallel sequencing (ChIP-seq) we showed that NKX3-1 colocalizes with the androgen receptor (AR) across the prostate cancer genome. We uncovered two distinct mechanisms by which NKX3-1 controls the AR transcriptional network in prostate cancer. First, NKX3-1 and AR directly regulate each other in a feed-forward regulatory loop. Second, NKX3-1 collaborates with AR and FoxA1 to mediate genes in advanced and recurrent prostate carcinoma. NKX3-1- and AR-coregulated genes include those found in the "protein trafficking" process, which integrates oncogenic signaling pathways. Moreover, we demonstrate that NKX3-1, AR, and FoxA1 promote prostate cancer cell survival by directly upregulating RAB3B, a member of the RAB GTPase family. Finally, we show that RAB3B is overexpressed in prostate cancer patients, suggesting that RAB3B together with AR, FoxA1, and NKX3-1 are important regulators of prostate cancer progression. Collectively, our work highlights a novel hierarchical transcriptional regulatory network between NKX3-1, AR, and the RAB GTPase signaling pathway that is critical for the genetic-molecular-phenotypic paradigm in androgen-dependent prostate cancer. © 2012, American Society for Microbiology.|
|Source Title:||Molecular and Cellular Biology|
|Appears in Collections:||Staff Publications|
Show full item record
Files in This Item:
There are no files associated with this item.
checked on Sep 21, 2018
WEB OF SCIENCETM
checked on Sep 11, 2018
checked on Jul 27, 2018
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.