Dataset Information

C1QBP Regulates YBX1 to Suppress the Androgen Receptor (AR)-Enhanced RCC Cell Invasion.

ABSTRACT: Early studies suggested that the androgen receptor (AR) might play important roles to promote the renal cell carcinoma (RCC) progression; however, the detailed mechanisms remain unclear. Here we demonstrated the higher YBX1 expression with lower C1QBP expression in human RCC clinical tissues, and the intensity of C1QBP was negatively correlated with the YBX1 nuclear expression. Mechanism dissection found C1QBP could interact with YBX1 to suppress the YBX1 activation via altering the YBX1 phosphorylation and nuclear translocation in RCC cells. The consequences of such suppression of YBX1 might then result in suppressing the RCC cell migration and invasion that involved altering the AR-modulated MMP9 signals. Interruption of this newly identified C1QBP?YBX1?AR?MMP9-suppressed RCC cell invasion pathway via targeting YBX1 or AR partially reversed the RCC cell invasion. Importantly, results from in vivo mouse model with orthotopic implantation of RCC OSRC2 cells into the left renal capsule also confirmed in vitro cell line studies showing targeting YBX1 could suppress RCC cell invasion via regulation of AR/MMP9 signals. Collectively, these data suggest that C1QBP could regulate YBX1 to suppress the AR-enhanced RCC cell invasion. Targeting this newly identified C1QBP/YBX1/AR/MMP9 signal pathway may provide a new potential therapy to better suppress RCC metastasis.

SUBMITTER: Yue D

PROVIDER: S-EPMC5247285 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature

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C1QBP Regulates YBX1 to Suppress the Androgen Receptor (AR)-Enhanced RCC Cell Invasion.

Yue Dan D Wang Yong Y Sun Yin Y Niu Yuanjie Y Chang Chawnshang C

Neoplasia (New York, N.Y.) 20170117 2

Early studies suggested that the androgen receptor (AR) might play important roles to promote the renal cell carcinoma (RCC) progression; however, the detailed mechanisms remain unclear. Here we demonstrated the higher YBX1 expression with lower C1QBP expression in human RCC clinical tissues, and the intensity of C1QBP was negatively correlated with the YBX1 nuclear expression. Mechanism dissection found C1QBP could interact with YBX1 to suppress the YBX1 activation via altering the YBX1 phospho ...[more]

PMID: 28107702

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Project description:Androgens control male sexual development and maintenance of the adult male phenotype. They have very divergent effects on their target organs like the reproductive organs, muscle, bone, brain and skin. This is explained in part by the fact that different cell types respond differently to androgen stimulus, even when all these responses are mediated by the same intracellular androgen receptor. To understand these tissue- and cell-specific readouts of androgens, we have to learn the many different steps in the transcription activation mechanisms of the androgen receptor (NR3C4). Like all nuclear receptors, the steroid receptors have a central DNA-binding domain connected to a ligand-binding domain by a hinge region. In addition, all steroid receptors have a relatively large amino-terminal domain. Despite the overall structural homology with other nuclear receptors, the androgen receptor has several specific characteristics which will be discussed here. This receptor can bind two types of androgen response elements (AREs): one type being similar to the classical GRE/PRE-type elements, the other type being the more divergent and more selective AREs. The hormone-binding domain has low intrinsic transactivation properties, a feature that correlates with the low affinity of this domain for the canonical LxxLL-bearing coactivators. For the androgen receptor, transcriptional activation involves the alternative recruitment of coactivators to different regions in the amino-terminal domain, as well as the hinge region. Finally, a very strong ligand-induced interaction between the amino-terminal domain and the ligand-binding domain of the androgen receptor seems to be involved in many aspects of its function as a transcription factor. This review describes the current knowledge on the structure-function relationships within the domains of the androgen receptor and tries to integrate the involvement of different domains, subdomains and motifs in the functioning of this receptor as a transcription factor with tissue- and cell-specific readouts.

Dataset Information

C1QBP Regulates YBX1 to Suppress the Androgen Receptor (AR)-Enhanced RCC Cell Invasion.

Publications

C1QBP Regulates YBX1 to Suppress the Androgen Receptor (AR)-Enhanced RCC Cell Invasion.

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