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.

Silencing of HJURP induces dysregulation of cell cycle and ROS metabolism in bladder cancer cells via PPARγ-SIRT1 feedback loop

“…Recent studies suggested that HJURP participated in the regulation of cell immortality in lung cancer 10 and breast cancer 11 , and could be a new independent prognostic marker for breast cancer 12 - 14 , indicating an important role of HJURP in human diseases 15 . Though the correlation between HJURP and bladder cancer has not been investigated yet, our transcriptome data 3 , 4 , 16 suggested that HJURP was involved in nucleosome assembly and cell cycle regulation in BCa. Our recent works showed that induction of cell cycle arrest could inhibit proliferation of urological cancer cells 17 - 19 .…”

PPARγ inhibition regulates the cell cycle, proliferation and motility of bladder cancer cells

“…Our group has revealed a variety of potential biomarkers 32,38,39 based on transcriptome data of normal bladder tissues vs BCa which has been demonstrated to play a crucial role in cancer cell invasion and migration. 52 The association of vimentin and cytokeratin was also revealed in the transitional cell carcinoma genesis of urinary bladder patients, and thus could be a favourable marker in the early diagnosis of transitional BCa.…”

“…Our group has revealed a variety of potential biomarkers 32,38,39 based on transcriptome data of normal bladder tissues vs BCa tissues. 34,41 Most of them are related to the PPAR signalling pathway, which could represent a connection between fatty acid/lipid metabolism and BCa.…”

Cephalosporin Antibiotics Specifically Enhance Conventional Chemotherapy in Nasopharyngeal Cancer

“…Lysosomal-associated protein multispanning transmembrane 5 (LAPTM5) is a membrane protein that localizes to intracellular vesicles. LAPTM5 mRNA level is frequently decreased in various cancer cell lines [28]. Overexpression of LAPTM5 in cancer cells induces lysosomal cell death due to lysosomal destabilization [29].…”