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Journal of Experimental & Clinical Cancer Research
Published in: Journal of Experimental & Clinical Cancer Research 1/2019

Open Access 01-12-2019 | Kidney Cancer | Research

The interaction of YBX1 with G3BP1 promotes renal cell carcinoma cell metastasis via YBX1/G3BP1-SPP1- NF-κB signaling axis

Authors: Yong Wang, Jing Su, Yiting Wang, Donghe Fu, Justin E. Ideozu, Hua Geng, Qiqi Cui, Chao Wang, Ruibing Chen, Yixi Yu, Yuanjie Niu, Dan Yue

Published in: Journal of Experimental & Clinical Cancer Research | Issue 1/2019

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Abstract

Background

Renal cell carcinoma (RCC) is a deadly urological tumor that remains largely incurable. Our limited understanding of key molecular mechanisms underlying RCC invasion and metastasis has hampered efforts to identify molecular drivers with therapeutic potential. With evidence from our previous study revealing that nuclear overexpression of YBX1 is associated with RCC T stage and metastasis, we investigated the effects of YBX1 in RCC migration, invasion, and adhesion, and then characterized its interaction with RCC-associated proteins G3BP1 and SPP1.

Methods

Renal cancer cell lines, human embryonic kidney cells, and clinical samples were analyzed to investigate the functional role of YBX1 in RCC metastasis. YBX1 knockdown cells were established via lentiviral infection and subjected to adhesion, transwell migration, and invasion assay. Microarray, immunoprecipitation, dual-luciferase reporter assay, and classical biochemical assays were applied to characterize the mechanism of YBX1 interaction with RCC-associated proteins G3BP1 and SPP1.

Results

Knockdown of YBX1 in RCC cells dramatically inhibited cell adhesion, migration, and invasion. Mechanistic investigations revealed that YBX1 interaction with G3BP1 upregulated their downstream target SPP1 in vitro and in vivo, which led to an activated NF-κB signaling pathway. Meanwhile, knockdown of SPP1 rescued the YBX1/G3BP1-mediated activation of NF-κB signaling pathway, and RCC cell migration and invasion. We further showed that YBX1 expression was positively correlated with G3BP1 and SPP1 expression levels in clinical RCC samples.

Conclusions

YBX1 interacts with G3BP1 to promote metastasis of RCC by activating the YBX1/G3BP1–SPP1–NF-κB signaling axis.
Appendix
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Metadata
Title
The interaction of YBX1 with G3BP1 promotes renal cell carcinoma cell metastasis via YBX1/G3BP1-SPP1- NF-κB signaling axis
Authors
Yong Wang
Jing Su
Yiting Wang
Donghe Fu
Justin E. Ideozu
Hua Geng
Qiqi Cui
Chao Wang
Ruibing Chen
Yixi Yu
Yuanjie Niu
Dan Yue
Publication date
01-12-2019
Publisher
BioMed Central
Published in
Journal of Experimental & Clinical Cancer Research / Issue 1/2019
Electronic ISSN: 1756-9966
DOI
https://doi.org/10.1186/s13046-019-1347-0

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