LAPTM4B promotes the progression of bladder cancer by stimulating cell proliferation and invasion

Yin,Yanhua; Fan,Yanyan; Yu,Gang; Du,Ying

doi:10.3892/ol.2021.13026

LAPTM4B promotes the progression of bladder cancer by stimulating cell proliferation and invasion

Authors:
- Yanhua Yin
- Yanyan Fan
- Gang Yu
- Ying Du
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Affiliations: Department of Pathology, Liaocheng People's Hospital, Liaocheng, Shandong 252000, P.R. China, Department of Public Health, Liaocheng Cancer Hospital, Liaocheng, Shandong 252000, P.R. China
Published online on: September 8, 2021 https://doi.org/10.3892/ol.2021.13026
Article Number: 765
Copyright: © Yin et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Bladder cancer is a highly metastatic tumor and one of the most common malignant tumors originating in the urinary system. Due to the complicated etiology and lack of significant early symptoms, the diagnosis and treatment of bladder cancer is difficult. Lysosome‑associated transmembrane protein 4β (LAPTM4B) was reported to be involved in the development and progression of several types of tumor, however, its potential effect on the development and metastasis of bladder cancer is still unclear. Immunohistochemistry was performed to detect the protein expression level of LAPTM4B in bladder cancer tissues and short hairpin RNAs targeting LAPTM4B were transfected into bladder cancer cells to knockdown its expression. MTT and colony formation assays were performed to detect cell proliferation, while wound healing and Transwell invasion assays were performed to detect cell migration and invasion, respectively. In addition, tumor growth assays were performed to confirm the effects of LAPTM4B in mice. The present study demonstrated that LAPTM4B was associated with the prognosis of patients with bladder cancer. In addition, LAPTM4B was associated with clinical characteristics, including tumor stage and recurrence. The results further showed that LAPTM4B knockdown could suppress the proliferation of bladder cancer cell lines. In addition, the migration and invasion of T24 and 5637 cells was suppressed following LAPTM4B knockdown in vitro. The in vivo data confirmed that knockdown of LAPTM4B markedly inhibited tumor growth and metastasis in mice. In summary, the results from the present study provide strong evidence of the effects of LAPTM4B in bladder cancer progression.

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1	Yao X, Li D, Xiong DM, Li L, Jiang R and Chen JX: A novel role of ribonuclease inhibitor in regulation of epithelial-to-mesenchymal transition and ILK signaling pathway in bladder cancer cells. Cell Tissue Res. 353:409–423. 2013. View Article : Google Scholar : PubMed/NCBI
2	Yang Y, Deng S, Zeng Q, Hu W and Chen T: Highly stable selenadiazole derivatives induce bladder cancer cell apoptosis and inhibit cell migration and invasion through the activation of ROS-mediated signaling pathways. Dalton Trans. 45:18465–18475. 2016. View Article : Google Scholar : PubMed/NCBI
3	Soria F, Krabbe LM, Todenhöfer T, Dobruch J, Mitra AP, Inman BA, Gust KM, Lotan Y and Shariat SF: Molecular markers in bladder cancer. World J Urol. 37:31–40. 2019. View Article : Google Scholar : PubMed/NCBI
4	Ferlay J, Colombet M, Soerjomataram I, Mathers C, Parkin DM, Piñeros M, Znaor A and Bray F: Estimating the global cancer incidence and mortality in 2018: GLOBOCAN sources and methods. Int J Cancer. 144:1941–1953. 2019. View Article : Google Scholar : PubMed/NCBI
5	Radosavljevic V and Belojevic G: Shortcomings in bladder cancer etiology research and a model for its prevention. Tumori. 100:1–8. 2014.PubMed/NCBI
6	Jordan EJ and Iyer G: Targeted therapy in advanced bladder cancer: What have we learned? Urol Clin North Am. 42253–262. (ix)2015. View Article : Google Scholar : PubMed/NCBI
7	Pan CX, Zhang H, Tepper CG, Lin TY, Davis RR, Keck J, Ghosh PM, Gill P, Airhart S, Bult C, et al: Development and characterization of bladder cancer patient-derived xenografts for molecularly guided targeted therapy. PLoS One. 10:e01343462015. View Article : Google Scholar : PubMed/NCBI
8	Hou T, Zhou L, Wang L, Kazobinka G, Zhang X and Chen Z: CLCA4 inhibits bladder cancer cell proliferation, migration, and invasion by suppressing the PI3K/AKT pathway. Oncotarget. 8:93001–93013. 2017. View Article : Google Scholar : PubMed/NCBI
9	Ciccarese C, Massari F, Blanca A, Tortora G, Montironi R, Cheng L, Scarpelli M, Raspollini MR, Vau N, Fonseca J and Lopez-Beltran A: Tp53 and its potential therapeutic role as a target in bladder cancer. Expert Opin Ther Targets. 21:401–414. 2017. View Article : Google Scholar : PubMed/NCBI
10	Blom T, Li S, Dichlberger A, Bäck N, Kim YA, Loizides-Mangold U, Riezman H, Bittman R and Ikonen E: LAPTM4B facilitates late endosomal ceramide export to control cell death pathways. Nat Chem Biol. 11:799–806. 2015. View Article : Google Scholar : PubMed/NCBI
11	Zhang H, Qi S, Zhang T, Wang A, Liu R, Guo J, Wang Y and Xu Y: miR-188-5p inhibits tumour growth and metastasis in prostate cancer by repressing LAPTM4B expression. Oncotarget. 6:6092–6104. 2015. View Article : Google Scholar : PubMed/NCBI
12	Li Y, Zhang Q, Tian R, Wang Q, Zhao JJ, Iglehart JD, Wang ZC and Richardson AL: Lysosomal transmembrane protein LAPTM4B promotes autophagy and tolerance to metabolic stress in cancer cells. Cancer Res. 71:7481–7489. 2011. View Article : Google Scholar : PubMed/NCBI
13	Zhou K, Dichlberger A, Martinez-Seara H, Nyholm TKM, Li S, Kim YA, Vattulainen I, Ikonen E and Blom T: A ceramide-regulated element in the late endosomal protein LAPTM4B controls amino acid transporter interaction. ACS Cent Sci. 4:548–558. 2018. View Article : Google Scholar : PubMed/NCBI
14	Meng Y, Wang L, Chen D, Chang Y, Zhang M, Xu JJ, Zhou R and Zhang QY: LAPTM4B: An oncogene in various solid tumors and its functions. Oncogene. 35:6359–6365. 2016. View Article : Google Scholar : PubMed/NCBI
15	Yang H, Xiong F, Qi R, Liu Z, Lin M, Rui J, Su J and Zhou R: LAPTM4B-35 is a novel prognostic factor of hepatocellular carcinoma. J Surg Oncol. 101:363–369. 2010. View Article : Google Scholar : PubMed/NCBI
16	Xiao M, Jia S, Wang H, Wang J, Huang Y and Li Z: Overexpression of LAPTM4B: An independent prognostic marker in breast cancer. J Cancer Res Clin Oncol. 139:661–667. 2013. View Article : Google Scholar : PubMed/NCBI
17	Zhang H, Tian B, Yu H, Yao H and Gao Z: LAPTM4B-35 protein as a potential therapeutic target in gastric cancer. Tumour Biol. 35:12737–12742. 2014. View Article : Google Scholar : PubMed/NCBI
18	Lebovitz CB, Robertson AG, Goya R, Jones SJ, Morin RD, Marra MA and Gorski SM: Cross-cancer profiling of molecular alterations within the human autophagy interaction network. Autophagy. 11:1668–1687. 2015. View Article : Google Scholar : PubMed/NCBI
19	Wang L, Meng Y, Xu JJ and Zhang QY: The transcription factor AP4 promotes oncogenic phenotypes and cisplatin resistance by regulating LAPTM4B expression. Mol Cancer Res. 16:857–868. 2018. View Article : Google Scholar : PubMed/NCBI
20	Tian M, Chen Y, Tian D, Qiao X, Ma Z and Li J: Beclin1 antagonizes LAPTM4B-mediated EGFR overactivation in gastric cancer cells. Gene. 626:48–53. 2017. View Article : Google Scholar : PubMed/NCBI
21	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
22	Yang Y, Zhao Z, Xie C and Zhao Y: Dual-targeting liposome modified by glutamic hexapeptide and folic acid for bone metastatic breast cancer. Chem Phys Lipids. 228:1048822020. View Article : Google Scholar : PubMed/NCBI
23	Mahdavifar N, Ghoncheh M, Pakzad R, Momenimovahed Z and Salehiniya H: Epidemiology, incidence and mortality of bladder cancer and their relationship with the development index in the world. Asian Pac J Cancer Prev. 17:381–386. 2016. View Article : Google Scholar : PubMed/NCBI
24	Jung HK, Kim S, Park RW, Park JY, Kim IS and Lee B: Bladder tumor-targeted delivery of pro-apoptotic peptide for cancer therapy. J Control Release. 235:259–267. 2016. View Article : Google Scholar : PubMed/NCBI
25	Hussain SA, Palmer DH, Syn WK, Sacco JJ, Greensmith RMD, Elmetwali T, Aachi V, Lloyd BH, Jithesh PV, Arrand J, et al: Gene expression profiling in bladder cancer identifies potential therapeutic targets. Int J Oncol. 50:1147–1159. 2017. View Article : Google Scholar : PubMed/NCBI
26	Chen MW, Wei XD, Shi X, Lu L, Zhang G, Huang Y and Hou J: LncRNA HIF1A-AS2 accelerates malignant phenotypes of renal carcinoma by modulating miR-30a-5p/SOX4 axis as a ceRNA. Cancer Biol Med. 18:587–603. 2021. View Article : Google Scholar : PubMed/NCBI
27	Chen M, Zhuang C, Liu Y, Li J, Dai F, Xia M, Zhan Y, Lin J, Chen Z, He A, et al: Tetracycline-inducible shRNA targeting antisense long non-coding RNA HIF1A-AS2 represses the malignant phenotypes of bladder cancer. Cancer Lett. 376:155–164. 2016. View Article : Google Scholar : PubMed/NCBI
28	Sun Z, Niu S, Xu F, Zhao W, Ma R and Chen M: CircAMOTL1 promotes tumorigenesis through miR-526b/SIK2 axis in cervical cancer. Front Cell Dev Biol. 8:5681902020. View Article : Google Scholar : PubMed/NCBI
29	Li S, Wang L, Meng Y, Chang Y, Xu J and Zhang Q: Increased levels of LAPTM4B, VEGF and survivin are correlated with tumor progression and poor prognosis in breast cancer patients. Oncotarget. 8:41282–41293. 2017. View Article : Google Scholar : PubMed/NCBI
30	Li L, Shan Y, Yang H, Zhang S, Lin M, Zhu P, Chen XY, Yi J, McNutt MA, Shao GZ and Zhou RL: Upregulation of LAPTM4B-35 promotes malignant transformation and tumorigenesis in L02 human liver cell line. Anat Rec (Hoboken). 294:1135–1142. 2011. View Article : Google Scholar : PubMed/NCBI
31	Li Y, Iglehart JD, Richardson AL and Wang ZC: The amplified cancer gene LAPTM4B promotes tumor growth and tolerance to stress through the induction of autophagy. Autophagy. 8:273–274. 2012. View Article : Google Scholar : PubMed/NCBI
32	Meng Y, Wang L, Xu J and Zhang Q: AP4 positively regulates LAPTM4B to promote hepatocellular carcinoma growth and metastasis, while reducing chemotherapy sensitivity. Mol Oncol. 12:373–390. 2018. View Article : Google Scholar : PubMed/NCBI
33	Meng F, Chen X, Song H and Lou G: LAPTM4B down regulation inhibits the proliferation, invasion and angiogenesis of HeLa cells in vitro. Cell Physiol Biochem. 37:890–900. 2015. View Article : Google Scholar : PubMed/NCBI
34	Xiao M, Yang S, Meng F, Qin Y, Yang Y, Jia S, Cai X, Li C, Huang Y and Ning X: LAPTM4B predicts axillary lymph node metastasis in breast cancer and promotes breast cancer cell aggressiveness in vitro. Cell Physiol Biochem. 41:1072–1082. 2017. View Article : Google Scholar : PubMed/NCBI
35	Dong X, Tamura K, Kobayashi D, Ando N, Sumita K and Maehara T: LAPTM4B-35 is a novel prognostic factor for glioblastoma. J Neurooncol. 132:295–303. 2017. View Article : Google Scholar : PubMed/NCBI
36	Li M, Zhou R, Shan Y, Li L, Wang L and Liu G: Targeting a novel cancer-driving protein (LAPTM4B-35) by a small molecule (ETS) to inhibit cancer growth and metastasis. Oncotarget. 7:58531–58542. 2016. View Article : Google Scholar : PubMed/NCBI