摘要
细胞内钙离子浓度的增加在许多癌症特征的建立起着关键作用,包括异常增殖、迁移、入侵、抗凋亡和抗血管再生。钙离子进入失调是一种最微妙的机制,通过这种机制癌细胞消灭同行并且获得自适应优势,从而在整个有机体实现肿瘤生长,血管生成和传播。组成型和激动剂诱导的钙内流可能被贮存依赖以及贮存独立钙离子进入路线介导。越来越多的证据表明,癌症细胞里不同亚型的基质互动分子(Stim)和Orai蛋白质,即Stim1,Stim2,Orai1和Orai3以这两种途径为基础。无论是Stim和Orai蛋白的表达还是活动都已被链接到在许多实体瘤肿瘤表型的发生和维持上 ,包括前列腺癌、乳腺癌、肾,食管,皮肤,大脑,大肠癌,肺和肝等器官癌症。这里,我们调查现有数据以支持Stim和Orai在肿瘤发生关系的参与度并针对癌症患者提供基本原理。此外,我们总结了新的药理学鉴定工具方面的进步,这些工具已成功用于临床医疗。
关键词: Stim
Current Medicinal Chemistry
Title:Targeting Stim and Orai Proteins as an Alternative Approach in Anticancer Therapy
Volume: 23 Issue: 30
Author(s): Francesco Moccia, Estella Zuccolo, Valentina Poletto, Ilaria Turin, Germano Guerra, Paolo Pedrazzoli, Vittorio Rosti and Camillo Porta, Daniela Montagna
Affiliation:
关键词: Stim
摘要: An increase in intracellular Ca2+ concentration plays a key role in the establishment of many cancer hallmarks, including aberrant proliferation, migration, invasion, resistance to apoptosis and angiogenesis. The dysregulation of Ca2+ entry is one of the most subtle mechanisms by which cancer cells overwhelm their normal counterparts and gain the adaptive advantages that result in tumour growth, vascularisation and dissemination throughout the organism. Both constitutive and agonist-induced Ca2+ influx may be mediated by store-dependent as well as store-independent Ca2+ entry routes. A growing body of evidences have shown that different isoforms of Stromal Interaction Molecules (Stim1) and Orai proteins, i.e. Stim1, Stim2, Orai1 and Orai3, underlie both pathways in cancer cells. The alteration in either the expression or the activity of Stim and Orai proteins has been linked to the onset and maintenance of tumour phenotype in many solid malignancies, including prostate, breast, kidney, esophageal, skin, brain, colorectal, lung and liver cancers. Herein, we survey the existing data in support of Stim and Orai involvement in tumourigenesis and provide the rationale to target them in cancer patients. Besides, we summarize the most recent advances in the identification of novel pharmacological tools that could be successfully used in clinical therapy.
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Francesco Moccia, Estella Zuccolo, Valentina Poletto, Ilaria Turin, Germano Guerra, Paolo Pedrazzoli, Vittorio Rosti and Camillo Porta, Daniela Montagna , Targeting Stim and Orai Proteins as an Alternative Approach in Anticancer Therapy, Current Medicinal Chemistry 2016; 23 (30) . https://dx.doi.org/10.2174/0929867323666160607111220
DOI https://dx.doi.org/10.2174/0929867323666160607111220 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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