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Quantitative proteomics discloses monacolin K-induced alterations in triple-negative breast cancer cell proteomes and phosphoproteomes.
Molecular Omics ( IF 3.0 ) Pub Date : 2020-02-17 , DOI: 10.1039/c9mo00140a Federica Del Gaudio 1 , Ida Chiara Guerrera , Raffaele Riccio , Maria Chiara Monti
Molecular Omics ( IF 3.0 ) Pub Date : 2020-02-17 , DOI: 10.1039/c9mo00140a Federica Del Gaudio 1 , Ida Chiara Guerrera , Raffaele Riccio , Maria Chiara Monti
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A positive prognosis of triple-negative breast cancer can be considered as one of the major challenges in clinical studies; accordingly, scientific research has the mission to find out novel chemotherapeutics to make it curable. In recent times, a good potential of dietary bioactive natural substances, called nutraceuticals, in suppressing cancer cell proliferation via gene expression regulation has been discovered: this effect and the lack of toxicity make nutraceuticals potentially effective agents against cancers. Monacolin K from red rice, a FDA-approved and well-tolerated compound generally employed to treat hypercholesterolemia, has been proved to have anti-proliferative and apoptotic effects in a wide panel of triple-negative breast cancers. Thus, an unbiased analysis of monacolin K-induced MDA-MB-231 cellular pathway alterations has been carried out by quantitative proteomics exploiting isobaric tags. Despite the positive modulation of some proteins already reported in the literature, an increased concentration of the tissue-type plasminogen activator PLAT has interestingly been found. This is a marker of good prognosis in mammary cancer, suggesting the anti-metastatic properties of this molecule as strongly associated with the alterations in the cytoskeleton organization and the consequent modulation of adhesion, motility and proteolysis. In accordance, some of the found monacolin K-induced phosphoproteome alterations have a tight connection to cell migration mechanisms. In this setting, the over-phosphorylation of Lamin A and of melanophilin induced by monacolin K has been very attractive. Moreover, monacolin K exerts its effect on the over-expression of the tissue inhibitor metalloproteinase-2 (TIMP-2), an endogenous metalloproteinase inhibitor. This protein modulates growth, migration and invasion of tumor cells and inhibits tumor angiogenesis.
中文翻译：
定量蛋白质组学揭示了莫那可林K诱导的三阴性乳腺癌细胞蛋白质组和磷酸化蛋白质组的变化。
三阴性乳腺癌的阳性预后可被认为是临床研究中的主要挑战之一。因此，科学研究的任务是找出新的化学疗法使其可治愈。近年来，人们发现饮食生物活性天然物质（营养食品）在通过基因表达调控抑制癌细胞增殖方面具有良好的潜力：这种作用和毒性的缺乏使营养食品成为对抗癌症的潜在有效药物。来自红米的莫纳可林K是一种经FDA批准且耐受性良好的化合物，通常用于治疗高胆固醇血症，已被证明在多种三阴性乳腺癌中具有抗增殖和凋亡作用。因此，通过定量蛋白质组学，利用同量异位标记对莫纳可林K诱导的MDA-MB-231细胞途径改变进行了无偏性分析。尽管已经报道了一些蛋白质的正调节作用，但是有趣的是发现组织型纤溶酶原激活物PLAT的浓度增加了。这是在乳腺癌中预后良好的标志，表明该分子的抗转移特性与细胞骨架组织的改变以及随之而来的粘附，运动性和蛋白水解的调节密切相关。因此，一些发现的莫纳可林K诱导的磷酸化蛋白质组改变与细胞迁移机制密切相关。在这种情况下，莫纳可林K诱导的层粘连蛋白A和嗜黑素蛋白的过度磷酸化非常吸引人。此外，莫纳可林K对内源性金属蛋白酶抑制剂组织抑制剂金属蛋白酶2（TIMP-2）的过表达发挥作用。该蛋白调节肿瘤细胞的生长，迁移和侵袭并抑制肿瘤血管生成。
更新日期：2020-02-18
中文翻译：
定量蛋白质组学揭示了莫那可林K诱导的三阴性乳腺癌细胞蛋白质组和磷酸化蛋白质组的变化。
三阴性乳腺癌的阳性预后可被认为是临床研究中的主要挑战之一。因此，科学研究的任务是找出新的化学疗法使其可治愈。近年来，人们发现饮食生物活性天然物质（营养食品）在通过基因表达调控抑制癌细胞增殖方面具有良好的潜力：这种作用和毒性的缺乏使营养食品成为对抗癌症的潜在有效药物。来自红米的莫纳可林K是一种经FDA批准且耐受性良好的化合物，通常用于治疗高胆固醇血症，已被证明在多种三阴性乳腺癌中具有抗增殖和凋亡作用。因此，通过定量蛋白质组学，利用同量异位标记对莫纳可林K诱导的MDA-MB-231细胞途径改变进行了无偏性分析。尽管已经报道了一些蛋白质的正调节作用，但是有趣的是发现组织型纤溶酶原激活物PLAT的浓度增加了。这是在乳腺癌中预后良好的标志，表明该分子的抗转移特性与细胞骨架组织的改变以及随之而来的粘附，运动性和蛋白水解的调节密切相关。因此，一些发现的莫纳可林K诱导的磷酸化蛋白质组改变与细胞迁移机制密切相关。在这种情况下，莫纳可林K诱导的层粘连蛋白A和嗜黑素蛋白的过度磷酸化非常吸引人。此外，莫纳可林K对内源性金属蛋白酶抑制剂组织抑制剂金属蛋白酶2（TIMP-2）的过表达发挥作用。该蛋白调节肿瘤细胞的生长，迁移和侵袭并抑制肿瘤血管生成。
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