Multifunctional Role of Astrocyte Elevated Gene-1 (AEG-1) in Cancer: Focus on Drug Resistance.
Multifunctional Role of Astrocyte Elevated Gene-1 (AEG-1) in Cancer: Focus on Drug Resistance.
复制标题
星形胶质细胞升高基因-1（AEG-1）在癌症中的多功能作用：关注耐药性。
DOI：
10.3390/cancers13081792
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发表时间：
2021-04-09
期刊：
影响因子：
5.2
通讯作者：
Sarkar D
中科院分区：
文献类型：
--
作者：
Manna D;Sarkar D
化疗是治疗癌症的主要方式。然而，癌细胞适应在压力条件下生存，在许多情况下，它们天生对化疗有抵抗力。此外，在对化疗产生初始反应后，存活的癌细胞获得新的改变，使其具有化疗耐药性。帮助癌细胞适应压力的基因通常有助于化学耐药，其中一个基因是星形胶质细胞升高基因-1 （AEG-1）。迄今为止研究的所有癌症中，AEG-1水平均升高，并且AEG-1有助于高度侵袭性、转移性癌症的发展。在这篇综述中，我们全面描述了AEG-1增强肿瘤发展的机制，并特别关注其调节化疗耐药的能力。我们还讨论了抑制AEG-1以克服化学耐药的潜在方法。癌症的发展是由于癌细胞本身获得了许多遗传和表观遗传改变，以及其微环境的持续变化。癌细胞的可塑性使其能够不断适应外源性环境压力、肿瘤内部环境和癌症治疗本身所带来的选择压力。对治疗的抵抗，无论是固有的还是在治疗开始后获得的，是肿瘤学家在努力有效地控制疾病时面临的主要障碍。化疗耐药是侵袭性癌症的重要标志，驱动癌基因诱导的信号通路和分子异常为化疗耐药创造了平台。癌基因星形胶质细胞升高基因-1/Metadherin （AEG-1/MTDH）在多种癌症中过表达，其过表达促进了癌症的所有特征，如增殖、侵袭、转移、血管生成和化疗耐药。本文综述了AEG-1促进肿瘤发生的分子机制，特别强调了其调节化学耐药的能力。
Chemotherapy is a major mode of treatment for cancers. However, cancer cells adapt to survive in stressful conditions and in many cases, they are inherently resistant to chemotherapy. Additionally, after initial response to chemotherapy, the surviving cancer cells acquire new alterations making them chemoresistant. Genes that help adapt the cancer cells to cope with stress often contribute to chemoresistance and one such gene is Astrocyte elevated gene-1 (AEG-1). AEG-1 levels are increased in all cancers studied to date and AEG-1 contributes to the development of highly aggressive, metastatic cancers. In this review, we provide a comprehensive description of the mechanism by which AEG-1 augments tumor development with special focus on its ability to regulate chemoresistance. We also discuss potential ways to inhibit AEG-1 to overcome chemoresistance. Cancer development results from the acquisition of numerous genetic and epigenetic alterations in cancer cells themselves, as well as continuous changes in their microenvironment. The plasticity of cancer cells allows them to continuously adapt to selective pressures brought forth by exogenous environmental stresses, the internal milieu of the tumor and cancer treatment itself. Resistance to treatment, either inherent or acquired after the commencement of treatment, is a major obstacle an oncologist confronts in an endeavor to efficiently manage the disease. Resistance to chemotherapy, chemoresistance, is an important hallmark of aggressive cancers, and driver oncogene-induced signaling pathways and molecular abnormalities create the platform for chemoresistance. The oncogene Astrocyte elevated gene-1/Metadherin (AEG-1/MTDH) is overexpressed in a diverse array of cancers, and its overexpression promotes all the hallmarks of cancer, such as proliferation, invasion, metastasis, angiogenesis and chemoresistance. The present review provides a comprehensive description of the molecular mechanism by which AEG-1 promotes tumorigenesis, with a special emphasis on its ability to regulate chemoresistance.
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