Upregulated GRB7 promotes proliferation and tumorigenesis of Bladder Cancer via Phospho-AKT Pathway

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Abstract

Growth factor receptor-bound protein 7 (GRB7) has been found closely related to the occurrence and development of various tumors, but its function in bladder cancer has not yet been elucidated. The study is aiming at investigating the expression and function of GRB7 in bladder cancer. The Cancer Genome Atlas (TCGA) database was selected to analyze mRNA levels of GRB7 in bladder cancer. RT-qPCR and Western blot were conducted to detect the expression of GRB7 in normal bladder epithelial cells, seven bladder cancer cell lines and eight pairs of malignant/nonmalignant bladder tissues. The role of GRB7 in tumor proliferation and tumorigenesis was explored by establishing stable cells, in vitro cell experiments and in vivo xenograft models. The molecular regulation mechanism of GRB7 in bladder cancer was investigated by treatment with AKT inhibitor. GRB7 mRNA was upregulated in bladder cancer samples compared with that in normal tissue samples. Overexpressing GRB7 significantly promoted the proliferation and tumorigenesis of bladder cancer. However, silencing GRB7 played the retarding part. GRB7 promoted G1/S transition by activating the AKT pathway. Our results indicate that GRB7 plays an important role in promoting proliferation and tumorigenesis of bladder cancer.

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PI3K/Akt signaling transduction pathway, erythropoiesis and glycolysis in hypoxia

Youbang Xie, Xuefeng Shi, Kuo Sheng … (2018)

The purpose of this review is to summarize the research progress of PI3K/Akt signaling pathway in erythropoiesis and glycolysis. Phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) is activated by numerous genes and leads to protein kinase B (Akt) binding to the cell membrane, with the help of phosphoinositide-dependent kinase, in the PI3K/Akt signal transduction pathway. Threonine and serine phosphorylation contribute to Akt translocation from the cytoplasm to the nucleus and further mediates enzymatic biological effects, including those involved in cell proliferation, apoptosis inhibition, cell migration, vesicle transport and cell cancerous transformation. As a key downstream protein of the PI3K/Akt signaling pathway, hypoxia-inducible factor (HIF)-1 is closely associated with the concentration of oxygen in the environment. Maintaining stable levels of HIF-1 protein is critical under normoxic conditions; however, HIF-1 levels quickly increase under hypoxic conditions. HIF-1α is involved in the acute hypoxic response associated with erythropoietin, whereas HIF-2α is associated with the response to chronic hypoxia. Furthermore, PI3K/Akt can reduce the synthesis of glycogen and increase glycolysis. Inhibition of glycogen synthase kinase 3β activity by phosphorylation of its N-terminal serine increases accumulation of cyclin D1, which promotes the cell cycle and improves cell proliferation through the PI3K/Akt signaling pathway. The PI3K/Akt signaling pathway is closely associated with a variety of enzymatic biological effects and glucose metabolism.

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Urinary Biomarkers for Diagnosis of Bladder Cancer

Sara E Grusing, Rongwei Fu, Katie S Gustafson … (2015)

Urinary biomarkers may be a useful alternative or adjunct to cystoscopy for diagnosis of bladder cancer.

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P53 as a prognostic marker for bladder cancer: a meta-analysis and review.

F Real, Juan Bustos, Ana Nascimento … (2005)

P53 is the most widely investigated molecular marker in bladder cancer. We aimed to review comprehensively the evidence for use of changes in P53 to predict bladder-cancer recurrence, progression, and mortality. We reviewed 168 publications from 117 studies. Estimates of significance were extracted from association tests, and hazard ratios with 95% CI from actuarial curves and Cox regression analyses. A meta-analysis was done on the studies that applied Cox models. The methods used to assess significance varied widely between studies. 27% (nine of 34) of studies that assessed the prognostic value of P53 overexpression in recurrence by use of multivariate tests showed a significant association. The corresponding values for progression and mortality were 50% (12 of 24) and 29% (ten of 35), respectively. In the studies that used Cox models, the overall risk of recurrence was 1.6 (95% CI 1.2-2.1), of progression was 3.1 (1.9-4.9), and of mortality was 1.4 (1.2-1.7). These findings could be overestimates because of publication and reporting bias. After 10 years of research, evidence is not sufficient to conclude whether changes in P53 act as markers of outcome in patients with bladder cancer.

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Author and article information

Journal

Journal ID (nlm-ta): Int J Biol Sci

Journal ID (iso-abbrev): Int J Biol Sci

Journal ID (publisher-id): ijbs

Title: International Journal of Biological Sciences

Publisher: Ivyspring International Publisher (Sydney )

ISSN (Electronic): 1449-2288

Publication date Collection: 2020

Publication date (Electronic): 23 October 2020

Volume: 16

Issue: 16

Pages: 3221-3230

Affiliations

[1 ]Department of Pathogen Biology and Immunology, School of Life Sciences and Biopharmaceutics, Guangdong Pharmaceutical University, Guangzhou 510006, China.

[2 ]Shenzhen Long-gang Maternal and Child Health Hospital Centralab, Shenzhen 518172, China.

[3 ]Department of Basic Medicine, Nanyang Medical College, Nanyang, Henan 473061, China.

[4 ]Department of Physiology, School of Life Sciences and Biopharmaceutics, Guangdong Pharmaceutical University, Guangzhou 510006, China.

[5 ]Guangdong Provincial Key Laboratory of Pharmaceutical Bioactive Substances, Guangdong Pharmaceutical University, Guangzhou 510006, China.

[6 ]KingMed School of Laboratory Medicine, Guangzhou Medical University, Guangzhou, Guangdong 510182, China.

[7 ]Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China.

Author notes

✉ Corresponding authors: Jie Yuan, E-mail: yuanjie@ 123456mail.sysu.edu.cn , Zhongshan School of Medicine, Sun Yat-sen University 74 Zhongshan Road II Guangzhou, Guangdong 510080, China, Tel: +86(20)87333587. Lan Wang, E-mail: wlwlan3435@ 123456163.com , Department of Pathogen Biology and Immunology, School of Life Sciences and Biopharmaceutics, Guangdong Pharmaceutical University, Guangdong 510006, China, Tel: 86-20-39352196.

*These authors contributed equally to this work.

Competing Interests: The authors have declared that no competing interest exists.

Article

Publisher ID: ijbsv16p3221

DOI: 10.7150/ijbs.49410

PMC ID: 7645994

PubMed ID: 33162827

SO-VID: b14b9219-c0ed-463d-ad25-1d1cc073f69a

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This is an open access article distributed under the terms of the Creative Commons Attribution License ( https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.

Upregulated GRB7 promotes proliferation and tumorigenesis of Bladder Cancer via Phospho-AKT Pathway

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Cancer Metabolism

Most cited references 33

PI3K/Akt signaling transduction pathway, erythropoiesis and glycolysis in hypoxia

Urinary Biomarkers for Diagnosis of Bladder Cancer

P53 as a prognostic marker for bladder cancer: a meta-analysis and review.

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