title: Downregulation of LAPTM5 suppresses cell proliferation and viability inducing cell cycle arrest at G0/G1 phase of bladder cancer cells.
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.
authors.affiliation: Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, P.R. China.
authors.forename: Liang
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, P.R. China.
authors.forename: Gang
authors.initials: G
authors.lastname: Wang
authors.affiliation: Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, P.R. China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Luo
authors.affiliation: Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, P.R. China.
authors.forename: Yongzhi
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, P.R. China.
authors.forename: Conghua
authors.initials: C
authors.lastname: Xie
authors.affiliation: Center for Medical Science Research, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Jiang
authors.affiliation: Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, P.R. China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Xiao
authors.affiliation: Department of Endocrinology, The First Affiliated Hospital of Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China.
authors.forename: Guofeng
authors.initials: G
authors.lastname: Qian
authors.affiliation: Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, P.R. China.
authors.forename: Xinghuan
authors.initials: X
authors.lastname: Wang
mesh_terms: D017209:Apoptosis / Q000235:genetics; D063646:Carcinogenesis / Q000235:genetics*; D059447:Cell Cycle Checkpoints / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D056827:Endosomal Sorting Complexes Required for Transport / Q000172:deficiency / Q000235:genetics; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D020935:MAP Kinase Signaling System / Q000235:genetics; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000235:genetics; D000075702:Nedd4 Ubiquitin Protein Ligases; D044767:Ubiquitin-Protein Ligases / Q000172:deficiency / Q000235:genetics; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000473:pathology; D048051:p38 Mitogen-Activated Protein Kinases / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D056827:Endosomal Sorting Complexes Required for Transport; D008565:Membrane Proteins; C100848:LAPTM5 protein, human; D000075702:Nedd4 Ubiquitin Protein Ligases; C000618483:Nedd4 protein, human; D044767:Ubiquitin-Protein Ligases; D048051:p38 Mitogen-Activated Protein Kinases