SH3BGRL2 inhibits growth and metastasis in clear cell renal cell carcinoma via activating hippo/TEAD1-Twist1 pathway
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 S...
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doaj-5177b1d5da8647b2968dc12f8c5bc55c2020-11-25T00:53:59ZengElsevierEBioMedicine2352-39642020-01-0151SH3BGRL2 inhibits growth and metastasis in clear cell renal cell carcinoma via activating hippo/TEAD1-Twist1 pathwayLei Yin0Wenjia Li1Aiming Xu2Heng Shi3Keyi Wang4Huan Yang5Ronghao Wang6Bo Peng7Department of Urology, Shanghai Tenth People's Hospital, School of Medicine in Tongji University, Shanghai, ChinaShanghai Institute of Cardiovascular Disease, Zhongshan Hospital, Fudan University, Shanghai, ChinaDepartment of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, ChinaDepartment of Urology, Shanghai Tenth People's Hospital, School of Medicine in Tongji University, Shanghai, ChinaDepartment of Urology, Shanghai Tenth People's Hospital, School of Medicine in Tongji University, Shanghai, ChinaDepartment of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Corresponding authors.School of basic medical sciences, Southwest Medical University, Luzhou, China; Corresponding authors.Department of Urology, Shanghai Tenth People's Hospital, School of Medicine in Tongji University, Shanghai, China; Corresponding authors.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, Twist1http://www.sciencedirect.com/science/article/pii/S2352396419308114 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Lei Yin Wenjia Li Aiming Xu Heng Shi Keyi Wang Huan Yang Ronghao Wang Bo Peng |
spellingShingle |
Lei Yin Wenjia Li Aiming Xu Heng Shi Keyi Wang Huan Yang Ronghao Wang Bo Peng SH3BGRL2 inhibits growth and metastasis in clear cell renal cell carcinoma via activating hippo/TEAD1-Twist1 pathway EBioMedicine |
author_facet |
Lei Yin Wenjia Li Aiming Xu Heng Shi Keyi Wang Huan Yang Ronghao Wang Bo Peng |
author_sort |
Lei Yin |
title |
SH3BGRL2 inhibits growth and metastasis in clear cell renal cell carcinoma via activating hippo/TEAD1-Twist1 pathway |
title_short |
SH3BGRL2 inhibits growth and metastasis in clear cell renal cell carcinoma via activating hippo/TEAD1-Twist1 pathway |
title_full |
SH3BGRL2 inhibits growth and metastasis in clear cell renal cell carcinoma via activating hippo/TEAD1-Twist1 pathway |
title_fullStr |
SH3BGRL2 inhibits growth and metastasis in clear cell renal cell carcinoma via activating hippo/TEAD1-Twist1 pathway |
title_full_unstemmed |
SH3BGRL2 inhibits growth and metastasis in clear cell renal cell carcinoma via activating hippo/TEAD1-Twist1 pathway |
title_sort |
sh3bgrl2 inhibits growth and metastasis in clear cell renal cell carcinoma via activating hippo/tead1-twist1 pathway |
publisher |
Elsevier |
series |
EBioMedicine |
issn |
2352-3964 |
publishDate |
2020-01-01 |
description |
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 |
url |
http://www.sciencedirect.com/science/article/pii/S2352396419308114 |
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