ONCOLOGY REPORTS
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2023
·Vol. 49
·期 3
·1-14
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IF 4.2
Sijia Han,Xueying Jin,Tianyu Hu,Feng Chi
Breast cancer remains the most common malignancy and the leading cause of cancer‑associated mortality in women worldwide. Lysosomal protein transmembrane 5 (LAPTM5), a lysosomal membrane protein, plays an important role in several human malignancies. However, the biological functions and mechanism of LAPTM5 in breast cancer remain unclear. In the present study, the potential tumor‑promoting effect of LAPTM5 was predicted by bioinformatics analysis. LAPTM5 was highly expressed in breast cancer clinical specimens. Moreover, in vitro studies demonstrated that cell proliferation, migration and invasion, as well as the process of epithelial‑mesenchymal transition (EMT) were promoted by LAPTM5 overexpression and were suppressed by LAPTM5 downregulation in vitro. The tumor‑promoting effects of LAPTM5 were also confirmed by xenograft tumor assay in vivo. It was found that the tumor‑promoting effects of LAPTM5 were partly dependent on the activation of the Wnt/β‑catenin signaling pathway. Furthermore, dual‑luciferase and chromatin immunoprecipitation assays verified that the transcription factor forkhead box protein 3 (FOXP3) directly bound to the promoter of LAPTM5 and negatively regulated its expression. Taken together, the present findings indicated that LAPTM5, negatively regulated by FOXP3, promoted the malignant phenotypes of breast cancer through activating the Wnt/β‑catenin signaling pathway.
研究领域:
肿瘤学
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分子生物学
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细胞生物学
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PubMed
高影响因子
Translational Cancer Research
·
2026
·Vol. 15
·期 3
·171
·
IF 2.1
Yan Zhang,Lu Lu,Qiuyu Zhao,Aiyu Ma,Meihua Jin,Xu Wang,Yuzhong Yang,Xuan Meng,Yiping Sun,Jinhua Zheng,Xiang Zheng
Background Lysosomal-associated protein transmembrane 5 (LAPTM5) is a transmembrane protein predominantly localized to late endosomes and lysosomes, with preferential expression in hematopoietic cells. Ferroptosis is an iron-dependent, non-apoptotic form of programmed cell death (PCD) that is driven by the lethal accumulation of lipid peroxides. Many studies have shown that ferroptosis is dependent on autophagy. Lipophagy is a selective form of autophagy by degrading lipid droplets (LDs) within autophagic vesicles to regulate lipid balance. Lipophagy can promote RAS-selective lethal 3 (RSL3)-induced ferroptosis. However, whether LAPTM5 regulates lipophagy to sensitize glioma cells to ferroptosis remains to be explored. Therefore, the objective of our study was to evaluate the potential role of LAPTM5 in ferroptosis. Methods The expression profile of LAPTM5 in human glioma tissues was analyzed by using The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) databases, and immunohistochemistry. Glioma cells were treated with ferroptosis inducer erastin, and then the cell viability, glutathione (GSH), and malondialdehyde (MDA) were detected. Lipophagy was tested by laser confocal microscopy and proteins expression were detected by western blot. Results Elevated expression of LAPTM5 was observed in glioma tissues compared to normal brain tissues, and its high expression level was associated with poorer patient prognosis. LAPTM5 promoted lipophagy in glioma cells. LAPTM5 enhanced the sensitivity of glioma cells to ferroptosis inducer erastin, while suppression of lipophagy inhibited LAPTM5-mediated sensitization to erastin. Conclusions The finding that glioma cells with high LAPTM5 expression were more sensitive to ferroptosis inducers suggests that glioma patients with high LAPTM5 expression may be more responsive to ferroptosis-inducing therapies.
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Cell Death & Disease
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2026
·
IF 12.2
Zeng Yuqing,He Chao,Chen Hongbo,Cheng Fang
Upregulation of autophagy in acute myeloid leukemia (AML) cells contributes to the development of resistance to cytarabine (AraC). LAPTM5 is mainly expressed in hematopoietic and immune cells, and has been associated with the progression of multiple cancers; however, its role in AML drug resistance remains uncharacterized. Here, we reanalyzed publicly available single-cell RNA sequencing (scRNA-seq) data from AML patients and found distinct gene expression profiles between AraC-resistant AML cells and untreated controls. Differentially expressed genes were significantly enriched in lysosome-related pathways, with LAPTM5 being highly expressed in drug-resistant cells, suggesting that it may be a key mediator of AraC resistance in AML. Mechanistically, AraC-resistant cells exhibited enhanced autophagic flux supported by LAPTM5-mediated upregulation of LAMP1 and LAMP2. Conversely, LAPTM5 knockdown impaired autophagolysosome formation by disrupting lysosomal biogenesis, thereby sensitizing resistant cells to AraC. These findings indicate that targeting LAPTM5 could enhance AraC sensitivity in AML by modulating autophagy. In vivo experiments further confirmed that the depletion of LAPTM5 inhibited tumor growth and synergistically suppressed AML progression with AraC. Collectively, our study identifies LAPTM5 as a critical regulator of AraC resistance via autophagy modulation, highlighting its potential as a therapeutic target for AML. In AML, AraC treatment induces LAPTM5 upregulation, which promotes LAMP1/2 transcription and lysosomal biogenesis. This facilitates autophagolysosome formation and enhances autophagic flux to reduce AraC-induced apoptosis, resulting in drug resistance. Targeting LAPTM5 represents a promising strategy to overcome this autophagy-mediated resistance.
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METABOLIC BRAIN DISEASE
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2026
·Vol. 41
·期 1
·148
·
IF 3.8
Li Ruomeng,Zhang Ting,Ren Dan,Zhu Hong,Xu Jiangxi,Xiao Lan
This study investigated the therapeutic potential and mechanism of Bushen Huoxue Acupuncture (BSHXA) against Alzheimer’s disease (AD) using integrated in vivo and in vitro approaches. In eight-month-old SAMP8 mice, BSHXA treatment significantly improved cognitive performance, alleviated hippocampal neuronal damage and neuroinflammation, and downregulated LAPTM5 expression. Complementary in vitro experiments in lipopolysaccharide (LPS)-stimulated BV2 microglia demonstrated that LAPTM5 knockdown reduced apoptosis, pathological protein accumulation, and pro-inflammatory M1 polarization. Through bioinformatic prediction and Co-IP assays, SMURF2 was identified as an E3 ubiquitin ligase directly interacting with LAPTM5 and promoting its ubiquitin-dependent degradation. SMURF2 overexpression in vitro reproduced protective effects similar to LAPTM5 knockdown. Importantly, in vivo knockdown of SMURF2 abolished the therapeutic benefits of BSHXA. Collectively, these findings demonstrate that BSHXA ameliorates AD progression by upregulating SMURF2, which promotes the ubiquitination and subsequent degradation of LAPTM5, thereby suppressing microglial M1 polarization, inhibiting neuroinflammatory responses, and attenuating AD pathologies. The SMURF2-LAPTM5 axis is established as a key mechanistic pathway underlying the neuroprotective effects of BSHXA. Graphical
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MOLECULAR NEUROBIOLOGY
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2023
·
IF 5.1
Hua Wei,Ma Shuainan,Pang Yuxin,Liu Qi,Wang Yueying,Liu Zhiyi,Zhao Nan,Ren Naixin,Jin Sinan,Wang Benshuai,Song Yuejia,Qi Jiping
Intracerebral hemorrhage (ICH) is a lethal stroke with high mortality or disability. However, effective therapy for ICH damage is generally lacking. Previous investigations have suggested that lysosomal protein transmembrane 5 (LAPTM5) is involved in various pathological processes, including autophagy, apoptosis, and inflammation. In this study, we aimed to identify the expression and functions of LAPTM5 in collagenase-induced ICH mouse models and hemoglobin-induced cell models. We found that LAPTM5 was highly expressed in brain tissues around the hematoma, and double immunostaining studies showed that LAPTM5 was co-expressed with microglia cells, neurons, and astrocytes. Following ICH, the mice presented increased brain edema, blood-brain barrier permeability, and neurological deficits, while pathological symptoms were alleviated after the LAPTM5 knockdown. Adeno-associated virus 9-mediated downregulation of LAPTM5 also improves ICH-induced secondary cerebral damage, including neuronal degeneration, the polarization of M1-like microglia, and inflammatory cascades. Furthermore, LAPTM5 promoted activation of the nuclear factor kappa-B (NF-κB) pathway in response to neuroinflammation. Further investigations indicated that brain injury improved by LAPTM5 knockdown was further exacerbated after the overexpression of receptor-interacting protein kinase 1 ( RIP1 ), which is revealed to trigger the NF-κB pathway. In vitro experiments demonstrated that LAPTM5 silencing inhibited hemoglobin-induced cell function and confirmed regulation between RIP1 and LAPTM5. In conclusion, the present study indicates that LAPTM5 may act as a positive regulator in the context of ICH by modulating the RIP1/NF-κB pathway. Thus, it may be a candidate gene for further study of molecular or therapeutic targets.
研究领域:
神经科学
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分子生物学
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病理生理学
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神经病学
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