JOURNAL OF FLUORESCENCE
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2026
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IF 3.4
Zhang Wei,Xu Jialin,Dong Liping,Wang Yong,Wu Yang
Extensive surgical resection improves survival in cancer patients. Fluorescence-guided imaging techniques have significantly enhanced the precision of cancer resections. Triple-negative breast cancer (TNBC) lacks expression of the estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2), and no other targetable molecules have been identified. In this study, we verified that the L-type amino acid transporter 1 (LAT1, also known as SLC7A5) is overexpressed in triple-negative breast cancer (TNBC) cells and we constructed a novel near-infrared fluorescent dye Cys-PEG 5 -IR target to SLC7A5. We then report the SLC7A5 receptor specificity of Cys-PEG 5 -IR as a contrast agent for TNBC imaging in vitro and in vivo. The conjugation elevated cell fluorescence on SLC7A5-overexpressing TNBC cells and produced minimal cell fluorescence when treated with SLC7A5 knockdown. Tumor uptake of Cys-PEG 5 -IR was significantly higher than the unlabeled IR in the subcutaneous MDA-MB-231 TNBC xenograft. This work highlights the prospect of using methionine (Met) transport pathway as an alternative strategy for targeting cancer cells, especially TNBC cells.
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高影响因子
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
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2026
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IF 2.5
Pengcheng Rao,Tairan Zhang,Ju Li,Weideng Wei,Xiaoqiang Xia,Qianming Chen,Xiaoping Xu,Xiaodong Feng
Cisplatin-based chemotherapy responses are highly heterogeneous across cancers, with the mechanisms governing drug sensitivity remaining incompletely understood. Using genome-wide CRISPR-Cas9 knockout screening, we systematically characterized regulators of cisplatin response and uncovered a counterintuitive finding: mTOR inhibition promotes cisplatin tolerance, contradicting the canonical view that PI3K-AKT-mTOR activation confers chemoresistance. Mechanistically, both mTOR suppression and cisplatin treatment converge to activate cytoprotective autophagy, which enhances cancer cell survival under therapeutic stress. The amino acid transporter SLC7A5 was identified and validated as a key integrator of the mTOR-autophagy axis that modulates cisplatin sensitivity. SLC7A5 expression positively correlates with cisplatin sensitivity across cancer cell lines, and its downregulation is associated with cisplatin resistance in multiple cancer types, supporting its potential as a mechanistically grounded predictive biomarker. Translationally, leucine supplementation sensitizes cancer cells to cisplatin in an SLC7A5-mTOR-autophagy-dependent manner. Collectively, our study defines a novel mTOR-autophagy adaptive loop governing cisplatin tolerance, positions SLC7A5 as a central regulatory node with both biomarker and therapeutic target value, and proposes leucine supplementation as a simple, translatable strategy to improve cisplatin efficacy in SLC7A5-expressing tumors.
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Bioactive Materials
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2021
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IF 14.593
Longfa Kou,Xinyu Jiang,Yingying Tang,Xing Xia,Yingtao Li,Aimin Cai,Hailun Zheng,Hailin Zhang,Vadivel Ganapathy,Qing Yao,Ruijie Chen
Reprogramed cellular metabolism is one of the most significant hallmarks of cancer. All cancer cells exhibit increased demand for specific amino acids, and become dependent on either an exogenous supply or upregulated de novo synthesis. The resultant enhanced availability of amino acids supports the reprogramed metabolic pathways and fuels the malignant growth and metastasis of cancers by providing energy and critical metabolic intermediates, facilitating anabolism, and activating signaling networks related to cell proliferation and growth. Therefore, pharmacologic blockade of amino acid entry into cancer cells is likely to have a detrimental effect on cancer cell growth. Here we developed a nanoplatform ( [email protected] ) to therapeutically target two transporters, SLC6A14 (ATB 0,+ ) and SLC7A5 (LAT1), that are known to be essential for the sustenance of amino acid metabolism in most cancers. The [email protected] uses tryptophan to guide SLC6A14-targeted delivery of JPH203, a high-affinity inhibitor of SLC7A5. In the process, SLC6A14 is also down-regulated. We tested the ability of this strategy to synergize with the anticancer efficacy of lapatinib, an inhibitor of EGFR/HER1/HER2-assocated kinase. These studies show that blockade of amino acid entry amplifies the anticancer effect of lapatinib via interference with mTOR signaling, promotion of apoptosis, and suppression of cell proliferation and metastasis. This represents the first study to evaluate the impact of amino acid starvation on the anticancer efficacy of widely used kinase inhibitor.
研究领域:
肿瘤学
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药理学
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纳米技术
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细胞生物学
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分子生物学
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Journal of Inflammation Research
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2025
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IF 4.1
Hua Jiang,Xiaotian Zhang,Shengyu Feng,Wei Feng
Background Parkinson’s disease (PD) is a progressive neurodegenerative disorder marked by motor dysfunction and dopaminergic neuron loss. Although its genetic and molecular underpinnings have been increasingly studied, the pathways driving PD progression remain unclear. The integrated stress response (ISR), a conserved mechanism activated by cellular stress, has been linked to several neurological diseases, but its role in PD and the key ISR-related genes involved are still poorly understood.Materials and Methods We used publicly available transcriptomic data from GEO, including single-cell RNA sequencing and spatial transcriptomics, to identify ISR-related genes involved in PD progression. ISR scores were compared across brain cell types, and differentially expressed genes in microglia were further screened using Lasso regression and random forest algorithms. Enrichment analyses (GSEA and GSVA) revealed their involvement in immune-related pathways. CIBERSORT was applied to assess immune cell infiltration, while spatial transcriptomics mapped the regional expression of key genes. Finally, DDIT4 expression was validated in PD cell and mouse models.Results We identified four key ISR-related genes (DDIT4, GNA13, HSPA1B, and SLC7A5) that were differentially expressed in PD microglia. Functional enrichment analysis revealed that these genes were predominantly involved in immune-related signaling pathways, including JAK-STAT, NF-κB, and Notch, suggesting their potential role in regulating neuroinflammation. Spatial transcriptomics revealed distinct regional expression patterns of these ISR-related genes across brain tissues. In vitro and in vivo experiments confirmed the upregulation of DDIT4 in PD models, and its silencing alleviated neurotoxicity and reduced α-synuclein aggregation, highlighting its potential role in PD pathogenesis.Conclusion This study provides new insights into the molecular mechanisms of PD and highlights DDIT4 as a promising therapeutic target. Its regulatory role in immune signaling and cellular stress pathways may offer novel avenues for clinical intervention and personalized treatment strategies in PD.
研究领域:
神经病学
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基因组学
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免疫学
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生物信息学
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神经退行性疾病
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转录组学
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JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
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2021
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IF 3.935
Zhongjian Chen,Yun Gao,Xiancong Huang,Yao Yao,Keke Chen,Su Zeng,Weimin Mao
Prognosis for esophageal squamous cell carcinoma (ESCC) is poor, so it is essential to develop a more complete understanding of the disease. The purpose of this study was to explore metabolic biomarkers and potential therapeutic targets for ESCC. An ultra-high-performance liquid chromatography coupled with high resolution mass (UPLC/MS)-based metabolomic analysis was performed in 141 ESCC cancerous tissue samples and 70 non-cancerous counterparts. The results showed that 41 differential metabolites were annotated in the training set, and 37 were validated in the test set. Single-metabolite-based receiver operating characteristic (ROC) curves as well as metabolite-based machine learning models, including Partial Least Squares (PLS), Support Vector Machine (SVM), and Random Forest (RF), were investigated for cancerous and non-cancerous tissue classification. Six most prevalent diagnostic metabolites—adenylsuccinic acid, UDP-GalNAc, maleylacetoacetic acid, hydroxyphenylacetylglycine, galactose, and kynurenine—showed testing predictive accuracies of 0.89, 0.95, 0.97, 0.89, 0.84, and 0.84, respectively. Moreover, the metabolite-based models (PLS, SVM, and RF) had testing predictive accuracies of 0.95, 0.95, and 1.00, respectively. Kaplan–Meier survival analysis and Cox proportional hazards regression analysis demonstrated that 2-hydroxymyristoylcarnitine (HR: 0.55, 95 % CI: 0.32 to 0.92), 3-hydroxyhexadecanoylcarnitine (HR: 0.49, 95 % CI: 0.29 to 0.83), and 2,3-Dinor-TXB1 (HR: 0.56, 95 % CI: 0.33 to 0.95) to be significantly associated with OS. Based on the observation of accumulation in amino acids, immunohistochemistry (IHC) staining revealed that the amino acid transporters SLC7A5/LAT1, SLC1A5/ASCT2, and SLC16A10/MCT10 were up-regulated in ESCC cancerous tissues when compared to non-cancerous equivalents. Consistently, the same panel of amino acids were downregulated in cells with SLC1A5 knockdown. Herein, it is concluded that this study not only identified several metabolites with diagnostic and/or prognostic value, but also provided accurate metabolite-based prediction models for ESCC tissue classification. Furthermore, the three up-regulated amino acid transporters were identified as potential therapeutic targets for ESCC, especially SLC1A5.
研究领域:
肿瘤学
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代谢组学
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生物信息学
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分子生物学
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癌症研究
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高影响因子
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