Elsevier

EBioMedicine

Volume 51, January 2020, 102596
EBioMedicine

Research paper
SH3BGRL2 inhibits growth and metastasis in clear cell renal cell carcinoma via activating hippo/TEAD1-Twist1 pathway

https://doi.org/10.1016/j.ebiom.2019.12.005Get rights and content
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open access

Abstract

Background

Clear cell renal cell carcinoma (ccRCC) is one of the most prevalent malignancies in the world, and tumor metastasis is still the main reason for disease progression. Accumulating evidence shows that SH3BGRL2 may play a key role in tumor progression and metastasis. However, the role of SH3BGRL2 in ccRCC has not been systematically investigated and remains elusive.

Methods

The clinical significance of SH3BGRL2 was evaluated by bioinformatic analysis and tissue microarray (TMA) samples. SH3BGRL2 expression was determined by RT-PCR, western blot and immunohistochemistry staining. Tumor suppressive effect of SH3BGRL2 was determined by both in vitro and in vivo studies. Western blot, chromatin immunoprecipitation assay and luciferase report assay were applied for mechanism dissection.

Findings

SH3BGRL2 was crucial for epithelial-mesenchymal transition (EMT) progression and metastasis in ccRCC. Clinically, SH3BGRL2 was identified as an independent prognostic factor for ccRCC patients. Gain- and loss-of-function results suggested that SH3BGRL2 played a critical role in cell proliferation, migration and invasion. Mechanistically, we found that SH3BGRL2 acted as a tumor suppressor through Hippo/TEAD1 signaling, then TEAD1 altered Twist1 expression at the transcriptional level via directly binding to its promoter region.

Interpretation

Our findings established that SH3BGRL2 performed as a tumor suppressor and modulator via Hippo/TEAD1-Twist1 signaling in ccRCC, and the alteration of SH3BGRL2 could serve as a functional response biomarker of tumor progression and metastasis in ccRCC.

Keywords

Clear cell renal cell carcinoma
SH3BGRL2
Metastasis
Hippo
Twist1
Abbreviations:ccRCC
Clear Cell Renal Cell Carcinoma
KIRC
Kidney Renal Clear Cell Carcinoma
TMA
Tissue Microarray
CHIP
Chromatin Immunoprecipitation Assay
IVIS
In Vivo Imaging System
ROC
Receiver Operating Characteristic
TCGA
The Cancer Genome Atlas
PDX
Patient-Derived Xenograft

Cited by (0)

1

These authors contributed equally to the study