Downregulation of LAPTM5 suppresses cell 
proliferation and viability inducing cell cycle 
arrest at G0/G1 phase of bladder cancer cells

Chen,Liang; Wang,Gang; Luo,Yi; Wang,Yongzhi; Xie,Conghua; Jiang,Wei; Xiao,Yu; Qian,Guofeng; Wang,Xinghuan

doi:10.3892/ijo.2016.3788

Downregulation of LAPTM5 suppresses cell proliferation and viability inducing cell cycle arrest at G0/G1 phase of bladder cancer cells

Authors:
- Liang Chen
- Gang Wang
- Yi Luo
- Yongzhi Wang
- Conghua Xie
- Wei Jiang
- Yu Xiao
- Guofeng Qian
- Xinghuan Wang
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Affiliations: Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, P.R. China, Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, P.R. China, Center for Medical Science Research, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, P.R. China, Department of Endocrinology, The First Affiliated Hospital of Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China
Published online on: December 5, 2016 https://doi.org/10.3892/ijo.2016.3788
Pages: 263-271

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Abstract

Our transcriptome analysis revealed in bladder cancer (BCa) tissues a significant induction of lysosomal-associated multispanning membrane protein 5 (LAPTM5), a lysosomal membrane protein preferentially expressing in immune cells and hematopoietic cells. Transportation of LAPTM5 from Golgi to lysosome could be inhibited by deficiency of Nedd4, a key member of E3 ubiquitin ligase family overexpressing in invasive BCa and promoting its progression. Therefore, we hypothesize that LAPTM5 may be closely correlated with BCa tumorigenesis. In human BCa tissues, we observed that LAPTM5 was significantly induced at both mRNA and protein levels, which is consistent with our microarray result. Furthermore, we established a BCa cell model with downregulated LAPTM5, revealing a significantly delayed growth rate in the BCa cells with knockdown of LAPTM5. Moreover, cell cycle arrest at G0/G1 phase was triggered by decreased LAPTM5 as well, which could lead to delayed BCa cell growth. In contrast, no significant alteration of apoptosis in the BCa cells with downregulated LAPTM5 was noticed. Analysis of the changes of migration and invasion, showed significant reduced LAPTM5 suppressed cell metastasis. Furthermore, proteins involved in epithelial-mesenchymal transition (EMT) were strongly altered, which plays a central role in metastasis. In addition, phosphorylated ERK1/2 and p38, key members of mitogen-activated protein kinase (MAPK) family regulating BCa tumorigenesis, were strongly decreased. Taken together, our results suggested that decreased LAPTM5 inhibited proliferation and viability, as well as induced G0/G1 cell cycle arrest possibly via deactivation of ERK1/2 and p38 in BCa cells.

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