Advanced Science
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2024
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IF 14.3
Guanyu Huang,Jiajun Zhang,Yu Xu,Fei Wu,Yiwei Fu,Xuelin Zhang,Hanxiao Yin,Yuanyuan You,Peng Zhao,Weihai Liu,Jingnan Shen,Junqiang Yin
LACTB is identified as a tumor suppressor in several tumors. However, preliminary study reveals that LACTB is overexpressed in osteosarcoma and indicates poor prognosis. Two missense mutations (rs34317102 and rs2729835) exist simultaneously in 92.31% of osteosarcoma patients and cause M5L and R469K double mutations in LACTB, suggesting the biologic function of LACTB protein may be altered in osteosarcoma. Moreover, LACTB M5L+R469K overexpression can promote malignant progression in different tumors, which suggests that the M5L and R469K mutations confer oncogene-like functions to LACTB. Mechanistically, LACTB M5L+R469K not only reduces the wild type p53 via enhancing PSMB7 catalytic activity, but also protects p53 R156P protein from lysosomal degradation, which suggesting LACTB M5L+R469K is a dual-regulator for wt-p53 and mutant p53, and derive oncogene-like functions. More importantly, clavulanate potassium, a bacterial β -lactamase inhibitor, can inhibit osteosarcoma proliferation and sensitize osteosarcoma to cisplatin by binding and blocking LACTB M5L+R469K . These findings revealed that the M5L and R469K double mutations can diminish the tumor suppressive ability of wild type LACTB and provide oncogene-like functions to LACTB. Inhibiting LACTB M5L+R469K can suppress the progression of osteosarcoma harbouring wild-type or mutant p53. Clavulanate potassium is a promising drug by targeting LACTB M5L+R469K -p53 pathway for the treatment of osteosarcoma patients.
研究领域:
肿瘤学
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遗传学
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分子生物学
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
DYES AND PIGMENTS
·
2025
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IF 4.2
Ya-Hui Zhou,Ru Yan,Kai Wang,Hong-Xia Xiang,Zhong-Yuan Cheng,Wei-Lai Jin
Acute lung injury (ALI) are serious respiratory disorders marked by compromised gas exchange, inflammation, and excessive extracellular matrix (ECM) deposition. Current imaging techniques remain limited for early detection and monitoring of these diseases. This study introduces HD-LACTB , a near-infrared fluorescent probe developed by conjugating a LACTB-targeting unit with a structurally optimized hemicyanine dye. This probe demonstrates high specificity, sensitivity, rapid response, and enhanced deep-tissue imaging performance compared to existing agents. It also enables mitochondrial-targeted intracellular imaging, allowing real-time visualization of LACTB dynamics during ALI progression and treatment. In cellular models, HD-LACTB detected LACTB expression levels with fluorescence intensity corresponding to disease severity. In murine models, it non-invasively tracked therapeutic efficacy, supporting its utility for evaluating interventions. HD-LACTB addresses a critical need in early diagnosis by providing a sensitive, non-invasive tool for real-time monitoring of disease progression and treatment response, thereby facilitating improved clinical decision-making and patient outcomes.
✓ 已验证
DOI
高影响因子
ANALYTICAL CHEMISTRY
·
2025
·
IF 6.7
Kai Wang,Lu Fan,Zhen-Zhen Pan,Yun Guo,Jie-Li Zhou
This study introduces HD-LACTB (Hemicyanine Dye-LACTB), a novel near-infrared fluorescent probe designed for real-time imaging of β-lactamase (LACTB) activity in nonsmall cell lung cancer (NSCLC). HD-LACTB incorporates a semicyanine-based signal-reporting unit that undergoes structural activation upon interaction with LACTB, enabling sensitive fluorescence detection. Compared to previous probes, HD-LACTB exhibits superior deep-tissue penetration, high selectivity, and low cytotoxicity, making it well-suited for in vivo applications. The probe effectively targets the mitochondria and enables intracellular imaging of LACTB activity during tumor induction and drug treatment. In both subcutaneous and orthotopic lung cancer mouse models, HD-LACTB demonstrated consistent and robust performance, accurately visualizing LACTB-mediated metabolic alterations. These results highlight the clinical potential of HD-LACTB as a noninvasive tool for early diagnosis, tumor staging, therapeutic monitoring, and personalized treatment assessment in NSCLC.
研究领域:
癌症研究
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生物成像
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分子诊断
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荧光探针
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诊疗一体化
✓ 已验证
DOI
PubMed
高影响因子
American Journal of Translational Research
·
2021
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IF 4.06
Fang Yang,Zhiqiang Yan,Wei Nie,Xingzhen Cheng,Zeying Liu,Wei Wang,Chunyan Shao,Gui Fu,Yanni Yu
Oxaliplatin (OXA), as a third-generation platinum anticancer drug, is a treatment drug for gastric cancer (GC). However, OXA resistance has become the main reason for OXA treatment failure. Serine beta-lactamase-like protein (LACTB), acts as a mitochondrial protein, can affect multiple cancer processes. Here, we aimed to investigate the function and mechanism of LACTB in OXA-resistant GC. After LACTB overexpression or autophagy activator (RAPA) treatment, cell proliferation, reactive oxygen species (ROS), apoptosis, mitochondrial dysfunction were evaluated through CCK-8 assay, Edu staining, flow cytometry and immunofluorescence assay. Moreover, DNA double-stranded damage and autophagy-related proteins were examined via western blot. We revealed that LACTB was downregulated in OXA-resistant MGC-803 cells, and overexpression of LACTB reduced the resistance of GC cells to OXA. Besides, our results uncovered that overexpression of LACTB induced apoptosis, reduced the mitochondrial membrane potential (MMP) and accelerated ROS accumulation in OXA-resistant MGC-803 (MGC-803/OXA) cells. Meanwhile, we verified that overexpression of LACTB decreased glucose uptake and ATP synthesis, induced mitochondria and DNA damages, and inhibited autophagy of MGC-803/OXA cells. Furthermore, our results certified that RAPA could weaken the function of LACTB on apoptosis and mitochondrial morphology and function in OXA-resistant MGC-803 cells with OXA treatment. Therefore, we demonstrated that LACTB could attenuate the resistance of MGC-803/OXA cells to OXA through autophagy-mediated mitochondrial morphological changes, mitochondrial dysfunction, and apoptosis, suggesting that LACTB, functions as a suppressor, is conducive to the therapy of OXA-resistant GC.
研究领域:
癌症生物学
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药理学
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细胞生物学
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分子生物学
✓ 已验证
DOI
PubMed
高影响因子
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