{"title":"Unravelling the oncogenic potential and prognostic significance of MAPT in breast cancer: An In-Silico inhibition of MAPT by paclitaxel","authors":"Asma Jan, Shazia Sofi, Manzoor Ahmad Mir","doi":"10.1016/j.adcanc.2025.100134","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><div>Breast cancer is the second top mortality of women globally. A major difficulty in therapeutic therapy is the disease's heterogeneity. However, modern discoveries in molecular biology and immunology have made it possible to create highly focused medicines for a variety of breast tumor subtypes. The fundamental aim of targeted treatments is to inhibit the growth of tumors by blocking the activity of a particular target or molecule. Morphological alterations in neuronal-glial cells have been linked to breast cancer (BC) on several occasions. However, the processes by which these neuronal proteins are regulated remain unclear despite their association with cancer. Analysis of the expression of genes in tissues of human BC has recognized microtubule-binding protein Tau to be a newly identified marker of response to paclitaxel and a modulator of paclitaxel sensitivity. In terms of taxane resistance pathways, those involving MAPs (microtubule-associated proteins) such as Tau are crucial. Reduced concentration of the Tau protein makes the microtubules of the mitochondrion and the cytoskeleton more vulnerable to the effects of the drug paclitaxel, which can disrupt mitosis and interfere with cell signalling. Clinical and preclinical data from the past several years support the hypothesis that ER induces the gene MAP-Tau and the resulting expression of the Tau protein influences the susceptibility of malignant cells to taxanes.</div></div><div><h3>Aim</h3><div>This study illustrates the expression pattern and prognostic significance of MAPT (Microtubule-Associated Proteins Tau) in BC and targeting MAPT using Paclitaxel drug.</div></div><div><h3>Methods</h3><div>The present study employed both <strong><em>In Silico</em></strong> and <strong><em>In Vitro</em></strong> methodologies to evaluate the expression profile, prognostic, and therapeutic value of the MAPT gene in BC and discover the interactions of MAPT in breast cancer pathogenesis.</div></div><div><h3>Results</h3><div>The <strong><em>In-Silico</em></strong> and <strong><em>In-Vitro</em></strong> studies have also revealed that patients with BC will have much better therapeutic responses when MAPT is inhibited in addition to normal therapies because overexpression of MAPT promotes tumor formation.</div></div><div><h3>Conclusion</h3><div>Overall, our research indicates that MAPT is associated with tumor growth in BC cells and its dysregulation has been implicated in breast cancer pathogenesis.</div></div>","PeriodicalId":72083,"journal":{"name":"Advances in cancer biology - metastasis","volume":"14 ","pages":"Article 100134"},"PeriodicalIF":2.0000,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Advances in cancer biology - metastasis","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2667394025000036","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"ONCOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Background
Breast cancer is the second top mortality of women globally. A major difficulty in therapeutic therapy is the disease's heterogeneity. However, modern discoveries in molecular biology and immunology have made it possible to create highly focused medicines for a variety of breast tumor subtypes. The fundamental aim of targeted treatments is to inhibit the growth of tumors by blocking the activity of a particular target or molecule. Morphological alterations in neuronal-glial cells have been linked to breast cancer (BC) on several occasions. However, the processes by which these neuronal proteins are regulated remain unclear despite their association with cancer. Analysis of the expression of genes in tissues of human BC has recognized microtubule-binding protein Tau to be a newly identified marker of response to paclitaxel and a modulator of paclitaxel sensitivity. In terms of taxane resistance pathways, those involving MAPs (microtubule-associated proteins) such as Tau are crucial. Reduced concentration of the Tau protein makes the microtubules of the mitochondrion and the cytoskeleton more vulnerable to the effects of the drug paclitaxel, which can disrupt mitosis and interfere with cell signalling. Clinical and preclinical data from the past several years support the hypothesis that ER induces the gene MAP-Tau and the resulting expression of the Tau protein influences the susceptibility of malignant cells to taxanes.
Aim
This study illustrates the expression pattern and prognostic significance of MAPT (Microtubule-Associated Proteins Tau) in BC and targeting MAPT using Paclitaxel drug.
Methods
The present study employed both In Silico and In Vitro methodologies to evaluate the expression profile, prognostic, and therapeutic value of the MAPT gene in BC and discover the interactions of MAPT in breast cancer pathogenesis.
Results
The In-Silico and In-Vitro studies have also revealed that patients with BC will have much better therapeutic responses when MAPT is inhibited in addition to normal therapies because overexpression of MAPT promotes tumor formation.
Conclusion
Overall, our research indicates that MAPT is associated with tumor growth in BC cells and its dysregulation has been implicated in breast cancer pathogenesis.
背景乳腺癌是全球女性死亡率第二高的疾病。这种疾病的异质性是治疗的一大难题。然而,现代分子生物学和免疫学的发现使得针对各种乳腺肿瘤亚型的高针对性药物成为可能。靶向治疗的根本目的是通过阻断特定靶点或分子的活性来抑制肿瘤的生长。神经元-胶质细胞的形态改变多次与乳腺癌(BC)有关。然而,尽管这些神经元蛋白与癌症有关,但其调节过程仍不清楚。对人类 BC 组织中基因表达的分析发现,微管结合蛋白 Tau 是新发现的紫杉醇反应标志物,也是紫杉醇敏感性的调节因子。就紫杉醇抗性途径而言,涉及 Tau 等微管相关蛋白(MAPs)的途径至关重要。Tau 蛋白浓度降低会使线粒体的微管和细胞骨架更容易受到紫杉醇药物的影响,从而破坏有丝分裂并干扰细胞信号。过去几年的临床和临床前数据支持ER诱导基因MAP-Tau,由此导致的Tau蛋白表达影响恶性细胞对紫杉类药物的易感性这一假设。方法本研究采用了体内和体外方法来评估 MAPT 基因在乳腺癌中的表达谱、预后和治疗价值,并发现 MAPT 在乳腺癌发病机制中的相互作用。结论总之,我们的研究表明,MAPT 与 BC 细胞中肿瘤的生长有关,它的失调与乳腺癌的发病机制有关。