Acylglycerol kinase promotes tumour growth and metastasis via activating the PI3K/AKT/GSK3β signalling pathway in renal cell carcinoma

Qian Zhu, Ai Lin Zhong, Hao Hu, Jing Jing Zhao, De Sheng Weng, Yan Tang, Qiu Zhong Pan, Zi Qi Zhou, Meng Jia Song, Jie Ying Yang, Jun Yi He, Yuan Liu, Min Li, Wan Ming Hu, Chao Pin Yang, Tong Xiang, Ming Yuan Chen, Gang Ma, Ling Guo, Jian Chuan Xia

Research output: Contribution to journalArticle

Abstract

BACKGROUND: Clinically, the median survival in patients with metastatic renal cell carcinoma (RCC) was only 6-12 months and a 5-year survival rate of less than 20%. Therefore, an in-depth study of the molecular mechanisms involved in RCC is of great significance for improving the survival of patients with advanced RCC. Acylglycerol kinase (AGK) is a newly discovered lipid kinase that has been reported to be a potent oncogene that may be involved in the regulation of malignant progression in a variety of tumours. However, the expression and biological characteristics of the AGK gene in RCC remain unclear. METHODS: AGK expression was quantified by quantitative real-time PCR, Western blotting and immunohistochemistry in RCC cell lines and paired patient tissues. Kaplan-Meier method and Cox proportional hazards models were used to evaluate the prognostic value of AGK in human RCC tissue samples. Chi-squared test was performed to analyse the correlation between AGK expression and the clinicopathological features. Stable overexpression and knockdown of AGK in RCC cells was constructed with lentivirus. The oncogenic effects of AGK in human RCC progression were investigated using assays of colony formation, anchorage-independent growth, EdU assay, cell cycle analysis, wound-healing, trans-well analysis and xenograft tumour model. GSEA and KEGG analysis were conducted to detect the potential pathway of AGK involved in RCC. These results were further confirmed using the luciferase reporter assays, immunofluorescence and in vivo experiments. RESULTS: AGK expression is significantly elevated in RCC and closely related to the malignant development and poor prognosis in RCC patients. By in vitro and in vivo experiments, AGK was shown to enhance the proliferation of RCC cells by promoting the transition from the G1 phase to the S phase in the cell cycle and to enhance the migration and invasion by promoting epithelial-mesenchymal transition. By activating the PI3K/AKT/GSK3β signalling pathway in RCC, AGK can increase nuclear accumulation of β-catenin, which further upregulated TCF/LEF transcription factor activity. CONCLUSIONS: AGK promotes the progression of RCC via activating the PI3K/AKT/GSK3β signalling pathway and might be a potential target for the further research of RCC.

Original languageEnglish (US)
Number of pages1
JournalJournal of hematology & oncology
Volume13
Issue number1
DOIs
StatePublished - Jan 3 2020

Fingerprint

acylglycerol kinase
Phosphatidylinositol 3-Kinases
Renal Cell Carcinoma
Neoplasm Metastasis
Growth
Neoplasms
TCF Transcription Factors

Keywords

  • AGK
  • AKT
  • Epithelial-mesenchymal transition
  • PI3K
  • Renal cell carcinoma

ASJC Scopus subject areas

  • Molecular Biology
  • Hematology
  • Oncology
  • Cancer Research

Cite this

Acylglycerol kinase promotes tumour growth and metastasis via activating the PI3K/AKT/GSK3β signalling pathway in renal cell carcinoma. / Zhu, Qian; Zhong, Ai Lin; Hu, Hao; Zhao, Jing Jing; Weng, De Sheng; Tang, Yan; Pan, Qiu Zhong; Zhou, Zi Qi; Song, Meng Jia; Yang, Jie Ying; He, Jun Yi; Liu, Yuan; Li, Min; Hu, Wan Ming; Yang, Chao Pin; Xiang, Tong; Chen, Ming Yuan; Ma, Gang; Guo, Ling; Xia, Jian Chuan.

In: Journal of hematology & oncology, Vol. 13, No. 1, 03.01.2020.

Research output: Contribution to journalArticle

Zhu, Q, Zhong, AL, Hu, H, Zhao, JJ, Weng, DS, Tang, Y, Pan, QZ, Zhou, ZQ, Song, MJ, Yang, JY, He, JY, Liu, Y, Li, M, Hu, WM, Yang, CP, Xiang, T, Chen, MY, Ma, G, Guo, L & Xia, JC 2020, 'Acylglycerol kinase promotes tumour growth and metastasis via activating the PI3K/AKT/GSK3β signalling pathway in renal cell carcinoma', Journal of hematology & oncology, vol. 13, no. 1. https://doi.org/10.1186/s13045-019-0840-4
Zhu, Qian ; Zhong, Ai Lin ; Hu, Hao ; Zhao, Jing Jing ; Weng, De Sheng ; Tang, Yan ; Pan, Qiu Zhong ; Zhou, Zi Qi ; Song, Meng Jia ; Yang, Jie Ying ; He, Jun Yi ; Liu, Yuan ; Li, Min ; Hu, Wan Ming ; Yang, Chao Pin ; Xiang, Tong ; Chen, Ming Yuan ; Ma, Gang ; Guo, Ling ; Xia, Jian Chuan. / Acylglycerol kinase promotes tumour growth and metastasis via activating the PI3K/AKT/GSK3β signalling pathway in renal cell carcinoma. In: Journal of hematology & oncology. 2020 ; Vol. 13, No. 1.
@article{f06e01a720c442adb94380a40e84835c,
title = "Acylglycerol kinase promotes tumour growth and metastasis via activating the PI3K/AKT/GSK3β signalling pathway in renal cell carcinoma",
abstract = "BACKGROUND: Clinically, the median survival in patients with metastatic renal cell carcinoma (RCC) was only 6-12 months and a 5-year survival rate of less than 20{\%}. Therefore, an in-depth study of the molecular mechanisms involved in RCC is of great significance for improving the survival of patients with advanced RCC. Acylglycerol kinase (AGK) is a newly discovered lipid kinase that has been reported to be a potent oncogene that may be involved in the regulation of malignant progression in a variety of tumours. However, the expression and biological characteristics of the AGK gene in RCC remain unclear. METHODS: AGK expression was quantified by quantitative real-time PCR, Western blotting and immunohistochemistry in RCC cell lines and paired patient tissues. Kaplan-Meier method and Cox proportional hazards models were used to evaluate the prognostic value of AGK in human RCC tissue samples. Chi-squared test was performed to analyse the correlation between AGK expression and the clinicopathological features. Stable overexpression and knockdown of AGK in RCC cells was constructed with lentivirus. The oncogenic effects of AGK in human RCC progression were investigated using assays of colony formation, anchorage-independent growth, EdU assay, cell cycle analysis, wound-healing, trans-well analysis and xenograft tumour model. GSEA and KEGG analysis were conducted to detect the potential pathway of AGK involved in RCC. These results were further confirmed using the luciferase reporter assays, immunofluorescence and in vivo experiments. RESULTS: AGK expression is significantly elevated in RCC and closely related to the malignant development and poor prognosis in RCC patients. By in vitro and in vivo experiments, AGK was shown to enhance the proliferation of RCC cells by promoting the transition from the G1 phase to the S phase in the cell cycle and to enhance the migration and invasion by promoting epithelial-mesenchymal transition. By activating the PI3K/AKT/GSK3β signalling pathway in RCC, AGK can increase nuclear accumulation of β-catenin, which further upregulated TCF/LEF transcription factor activity. CONCLUSIONS: AGK promotes the progression of RCC via activating the PI3K/AKT/GSK3β signalling pathway and might be a potential target for the further research of RCC.",
keywords = "AGK, AKT, Epithelial-mesenchymal transition, PI3K, Renal cell carcinoma",
author = "Qian Zhu and Zhong, {Ai Lin} and Hao Hu and Zhao, {Jing Jing} and Weng, {De Sheng} and Yan Tang and Pan, {Qiu Zhong} and Zhou, {Zi Qi} and Song, {Meng Jia} and Yang, {Jie Ying} and He, {Jun Yi} and Yuan Liu and Min Li and Hu, {Wan Ming} and Yang, {Chao Pin} and Tong Xiang and Chen, {Ming Yuan} and Gang Ma and Ling Guo and Xia, {Jian Chuan}",
year = "2020",
month = "1",
day = "3",
doi = "10.1186/s13045-019-0840-4",
language = "English (US)",
volume = "13",
journal = "Journal of Hematology and Oncology",
issn = "1756-8722",
publisher = "BioMed Central",
number = "1",

}

TY - JOUR

T1 - Acylglycerol kinase promotes tumour growth and metastasis via activating the PI3K/AKT/GSK3β signalling pathway in renal cell carcinoma

AU - Zhu, Qian

AU - Zhong, Ai Lin

AU - Hu, Hao

AU - Zhao, Jing Jing

AU - Weng, De Sheng

AU - Tang, Yan

AU - Pan, Qiu Zhong

AU - Zhou, Zi Qi

AU - Song, Meng Jia

AU - Yang, Jie Ying

AU - He, Jun Yi

AU - Liu, Yuan

AU - Li, Min

AU - Hu, Wan Ming

AU - Yang, Chao Pin

AU - Xiang, Tong

AU - Chen, Ming Yuan

AU - Ma, Gang

AU - Guo, Ling

AU - Xia, Jian Chuan

PY - 2020/1/3

Y1 - 2020/1/3

N2 - BACKGROUND: Clinically, the median survival in patients with metastatic renal cell carcinoma (RCC) was only 6-12 months and a 5-year survival rate of less than 20%. Therefore, an in-depth study of the molecular mechanisms involved in RCC is of great significance for improving the survival of patients with advanced RCC. Acylglycerol kinase (AGK) is a newly discovered lipid kinase that has been reported to be a potent oncogene that may be involved in the regulation of malignant progression in a variety of tumours. However, the expression and biological characteristics of the AGK gene in RCC remain unclear. METHODS: AGK expression was quantified by quantitative real-time PCR, Western blotting and immunohistochemistry in RCC cell lines and paired patient tissues. Kaplan-Meier method and Cox proportional hazards models were used to evaluate the prognostic value of AGK in human RCC tissue samples. Chi-squared test was performed to analyse the correlation between AGK expression and the clinicopathological features. Stable overexpression and knockdown of AGK in RCC cells was constructed with lentivirus. The oncogenic effects of AGK in human RCC progression were investigated using assays of colony formation, anchorage-independent growth, EdU assay, cell cycle analysis, wound-healing, trans-well analysis and xenograft tumour model. GSEA and KEGG analysis were conducted to detect the potential pathway of AGK involved in RCC. These results were further confirmed using the luciferase reporter assays, immunofluorescence and in vivo experiments. RESULTS: AGK expression is significantly elevated in RCC and closely related to the malignant development and poor prognosis in RCC patients. By in vitro and in vivo experiments, AGK was shown to enhance the proliferation of RCC cells by promoting the transition from the G1 phase to the S phase in the cell cycle and to enhance the migration and invasion by promoting epithelial-mesenchymal transition. By activating the PI3K/AKT/GSK3β signalling pathway in RCC, AGK can increase nuclear accumulation of β-catenin, which further upregulated TCF/LEF transcription factor activity. CONCLUSIONS: AGK promotes the progression of RCC via activating the PI3K/AKT/GSK3β signalling pathway and might be a potential target for the further research of RCC.

AB - BACKGROUND: Clinically, the median survival in patients with metastatic renal cell carcinoma (RCC) was only 6-12 months and a 5-year survival rate of less than 20%. Therefore, an in-depth study of the molecular mechanisms involved in RCC is of great significance for improving the survival of patients with advanced RCC. Acylglycerol kinase (AGK) is a newly discovered lipid kinase that has been reported to be a potent oncogene that may be involved in the regulation of malignant progression in a variety of tumours. However, the expression and biological characteristics of the AGK gene in RCC remain unclear. METHODS: AGK expression was quantified by quantitative real-time PCR, Western blotting and immunohistochemistry in RCC cell lines and paired patient tissues. Kaplan-Meier method and Cox proportional hazards models were used to evaluate the prognostic value of AGK in human RCC tissue samples. Chi-squared test was performed to analyse the correlation between AGK expression and the clinicopathological features. Stable overexpression and knockdown of AGK in RCC cells was constructed with lentivirus. The oncogenic effects of AGK in human RCC progression were investigated using assays of colony formation, anchorage-independent growth, EdU assay, cell cycle analysis, wound-healing, trans-well analysis and xenograft tumour model. GSEA and KEGG analysis were conducted to detect the potential pathway of AGK involved in RCC. These results were further confirmed using the luciferase reporter assays, immunofluorescence and in vivo experiments. RESULTS: AGK expression is significantly elevated in RCC and closely related to the malignant development and poor prognosis in RCC patients. By in vitro and in vivo experiments, AGK was shown to enhance the proliferation of RCC cells by promoting the transition from the G1 phase to the S phase in the cell cycle and to enhance the migration and invasion by promoting epithelial-mesenchymal transition. By activating the PI3K/AKT/GSK3β signalling pathway in RCC, AGK can increase nuclear accumulation of β-catenin, which further upregulated TCF/LEF transcription factor activity. CONCLUSIONS: AGK promotes the progression of RCC via activating the PI3K/AKT/GSK3β signalling pathway and might be a potential target for the further research of RCC.

KW - AGK

KW - AKT

KW - Epithelial-mesenchymal transition

KW - PI3K

KW - Renal cell carcinoma

UR - http://www.scopus.com/inward/record.url?scp=85077479975&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85077479975&partnerID=8YFLogxK

U2 - 10.1186/s13045-019-0840-4

DO - 10.1186/s13045-019-0840-4

M3 - Article

C2 - 31900208

AN - SCOPUS:85077479975

VL - 13

JO - Journal of Hematology and Oncology

JF - Journal of Hematology and Oncology

SN - 1756-8722

IS - 1

ER -