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Title: Integration of regulatory networks by NKX3-1 promotes androgen-dependent prostate cancer survival
Authors: Tan, Peck Yean
Chang, Cheng Wei
Chng, Kern Rei
Wansa, K. D. Senali Abayratna
Sung, Wing-Kin
Cheung, Edwin
Keywords: DRNTU::Science::Biological sciences
Issue Date: 2012
Source: Tan, P. Y., Chang, C. W., Chng, K. R., Wansa, K. D. S. A., 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.
Series/Report no.: Molecular and cellular biology
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.
DOI: 10.1128/MCB.05958-11
Rights: © 2012 American Society for Microbiology.
Fulltext Permission: none
Fulltext Availability: No Fulltext
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