LAPTM4B: an oncogene in various solid tumors and its functions

Zhang, Meng; Wang, L; D, Chen; Chang, Yanli; Zhang, M; Jj, Xu; Zhou, Ruanbao; Qy, Zhang

doi:10.1038/onc.2016.189

Cited by 62 publications

(67 citation statements)

References 58 publications

(65 reference statements)

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“…LAPTM4B (the lysosome-associated protein transmembrane-4b gene) is considered as an oncogene, and its overexpression has been proven to promote the proliferation of various tumor cells, boost invasion and metastasis, resist apoptosis, initiate autophagy, and assist drug resistance. [35][36][37][38] Overexpression of LAPTM4B in breast cancer cells results in resistance to anthracycline, and its knockdown can sensitize the drug response. 39 NGFRAP1 (nerve growth factor receptor-associated protein 1) is an apoptosisrelated gene, and its expression is downregulated in some solid organ malignancies and chronic lymphocytic leukemia.…”

Section: Discussionmentioning

confidence: 99%

A 4-gene leukemic stem cell score can independently predict the prognosis of myelodysplastic syndrome patients

Wang

Lin

Yao³

et al. 2020

Blood Advances

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Myelodysplastic syndrome (MDS) comprised a heterogeneous group of diseases. The prognosis of patients varies even in the same risk groups. Searching for novel prognostic markers is warranted. Leukemic stem cells (LSCs) are responsible for chemoresistance and relapse in leukemia. Recently, expressions of 17 genes related to stemness of LSCs were found to be associated with prognosis in acute myeloid leukemia patients. However, the clinical impact of LSC genes expressions in MDS, a disorder arising from hematopoietic stem cells, remains unclear. We analyzed expression profile of the 17 stemness-related genes in primary MDS patients and identified expression of 4 genes (LAPTM4B, NGFRAP1, EMP1, and CPXM1) were significantly correlated with overall survival (OS). We constructed an LSC4 scoring system based on the weighted sums of the expression of 4 genes and explored its clinical implications in MDS patients. Higher LSC4 scores were associated with higher revised International Prognostic Scoring System (IPSS-R) scores, complex cytogenetics, and mutations in RUNX1, ASXL1, and TP53. High-score patients had significantly shorter OS and leukemia-free survival (LFS), which was also confirmed in 2 independent validation cohorts. Subgroup analysis revealed the prognostic significance of LSC4 scores for OS remained valid across IPSS-R lower- and higher-risk groups. Furthermore, higher LSC4 score was an independent adverse risk factor for OS and LFS in multivariate analysis. In summary, LSC4 score can independently predict prognosis in MDS patients irrespective of IPSS-R risks and may be used to guide the treatment of MDS patients, especially lower-risk group in whom usually only supportive treatment is given.

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Section: Discussionmentioning

confidence: 99%

A 4-gene leukemic stem cell score can independently predict the prognosis of myelodysplastic syndrome patients

Wang

Lin

Yao³

et al. 2020

Blood Advances

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“…LAPTM4B has been identified as a direct target of miR-188-5p in PC3 and LNCaP cells (125) (Figure 4). LAPTM4B is located in late endosomes and lysosomes and can promote proliferation, invasion and inhibit apoptosis and is able to initiate autophagy (126). LAPTM4B is associated with poor prognosis and metastasis in several types of tumors (127)(128)(129)(130).…”

Section: Mir-188-5p Targets Lysosome Transmembrane Protein 4 (Laptm4b)mentioning

confidence: 99%

The Functional Role of Prostate Cancer Metastasis-related Micro-RNAs

Weidle

Epp

Birzele

et al. 2018

Cancer Genomics Proteomics

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The mortality of patients with hormone-resistant prostate cancer can be ascribed to a large degree to metastasis to distant organs, predominantly to the bones. In this review, we discuss the contribution of micro-RNAs (miRs) to the metastatic process of prostate cancer. The criteria for selection of miRs for this review were the availability of preclinical in vivo metastasis-related data in conjunction with prognostic clinical data. Depending on their function in the metastatic process, the corresponding miRs are up-or downregulated in prostate cancer tissues when compared to matching normal tissues. Up-regulated miRs preferentially target suppressors of cytokine signaling or tumor suppressorrelated genes and metastasis-inhibitory transcription factors. Down-regulated miRs promote epithelial-mesenchymal transition or mesenchymal-epithelial transition and diverse pro-metastatic signaling pathways. Some of the discussed miRs exert their function by simultaneously targeting epigenetic pathways as well as cell-cycle-related, antiapoptotic and signaling-promoting targets. Finally, we discuss potential therapeutic options for the treatment of prostate cancer-related metastases by substitution or inhibition of miRs. In 2017, 160,000 new cases of prostate cancer (PC) were diagnosed in the US and an equal number in the EU with 27,000 patients dying due to metastatic PC in the US and the EU (1). Localized disease can be potentially cured by therapies such as surgery and radiation, but in some patients, the disease progresses despite these therapies (2). Androgendeprivation therapy leads to long-lasting responses between 2 and 3 years, however the disease inevitably progresses to castration-resistant prostate cancer (CRPC) that is associated with metastatic disease and poor prognosis. Over the past 5 years, five drugs have been approved for treatment of CRPC (2). These are cabazitaxel, a taxane-based cytostatic; radium 223, an α-emitter; enzalutamide, a small-molecule androgen receptor (AR) antagonist; abiraterone, a blocker of de novo synthesis of androgens; and Sipuleucel, a dendritic cell-based immunotherapy (3). The recent genetic classification of PC has revealed seven subtypes and new molecular targets for molecular intervention such as vets erythroblastosis virus E26 homolog (ETS) family transcription factor-based fusion proteins as well as mutations in speckle-type POZ protein (SPOP), forkhead protein A1 (FOXA1) and isocitrate dehydrogenase 1 (IDH1) (4). The serine protease inhibitor Kazal-type 1 (SPINK), which is up-regulated in ETSrearrangement-negative tumors, is also being pursued as a new target for treatment of CRPC (5). Nucleic acid-based therapy is another approach for treatment of CRPC. Custirsen, a second-generation phosphorothioate antisense oligonucleotide targeting clusterin mRNA is presently undergoing phase III clinical studies in combination with chemotherapy in patients with CRPC (6, 7). Clusterin is upregulated in patients with CRPC and functions as an ATPindependent molecular chaperone with anti-a...

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“…Lysosomal‐associated protein transmembrane‐4 beta (LAPTM4B) is a high‐expression gene in hepatocellular carcinoma (HCC) cells identified by fluorescent‐differential display (Shao et al ., ; Liu et al ., ; Meng et al ., ). Previous studies have identified two alleles of the LAPTM4B gene, which are differentiated from one another by an extra tandem arranged 19‐bp sequence at the 5′ untranslated region (5′UTR) in the first exon in allele*2.…”

Section: Introductionmentioning

confidence: 99%

AP4 positively regulates LAPTM4B to promote hepatocellular carcinoma growth and metastasis, while reducing chemotherapy sensitivity

Yue

Wang

et al. 2018

Molecular Oncology

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Polymorphisms of the lysosomal‐associated protein transmembrane‐4 beta (LAPTM4B) gene are related to various forms of tumour susceptibility, which led us to hypothesize that some unique transcription factors targeting this polymorphism region may affect the biological function of LAPTM4B in tumour progression. In this study, we found that the transcription factor AP4 directly binds to the polymorphism region of the LAPTM4B gene promoter and induces its transcription. In addition, we demonstrated that AP4 promotes hepatocellular carcinoma (HCC) cell proliferation and metastasis and depresses chemotherapy sensitivity via LAPTM4B by activating the PI3K/AKT signalling pathway and caspase‐dependent pathway. Interestingly, we found that AP4 could not only regulate LAPTM4B by directly binding to the promoter, but also be regulated via a positive feedback mechanism involving LAPTM4B acting on c‐myc. Finally, we showed that AP4 and LAPTM4B are highly coexpressed in HCC tissues, and their coexpression may be a marker of poor prognosis. These findings provide evidence of the expression and functional coupling between AP4 and LAPTM4B and shed light on the regulation of LAPTM4B and its function in liver cancer.

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LAPTM4B: an oncogene in various solid tumors and its functions

Cited by 62 publications

References 58 publications

A 4-gene leukemic stem cell score can independently predict the prognosis of myelodysplastic syndrome patients

A 4-gene leukemic stem cell score can independently predict the prognosis of myelodysplastic syndrome patients

The Functional Role of Prostate Cancer Metastasis-related Micro-RNAs

AP4 positively regulates LAPTM4B to promote hepatocellular carcinoma growth and metastasis, while reducing chemotherapy sensitivity

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