The interaction of YBX1 with G3BP1 promotes renal cell carcinoma cell metastasis via YBX1/G3BP1-SPP1- NF-κB signaling axis
Posted on 2019-09-04 - 04:54
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.
CITE THIS COLLECTION
DataCite
3 Biotech
3D Printing in Medicine
3D Research
3D-Printed Materials and Systems
4OR
AAPG Bulletin
AAPS Open
AAPS PharmSciTech
Abhandlungen aus dem Mathematischen Seminar der Universität Hamburg
ABI Technik (German)
Academic Medicine
Academic Pediatrics
Academic Psychiatry
Academic Questions
Academy of Management Discoveries
Academy of Management Journal
Academy of Management Learning and Education
Academy of Management Perspectives
Academy of Management Proceedings
Academy of Management Review
Wang, Yong; Su, Jing; Wang, Yiting; Fu, Donghe; Ideozu, Justin; Geng, Hua; et al. (2019). The interaction of YBX1 with G3BP1 promotes renal cell carcinoma cell metastasis via YBX1/G3BP1-SPP1- NF-κB signaling axis. figshare. Collection. https://doi.org/10.6084/m9.figshare.c.4653125.v1
or
Select your citation style and then place your mouse over the citation text to select it.
SHARE
Usage metrics
Read the peer-reviewed publication
AUTHORS (12)
YW
Yong Wang
JS
Jing Su
YW
Yiting Wang
DF
Donghe Fu
JI
Justin Ideozu
HG
Hua Geng
QC
Qiqi Cui
CW
Chao Wang
RC
Ruibing Chen
YY
Yixi Yu
YN
Yuanjie Niu
DY
Dan Yue