Manna Debashri, Sarkar Devanand
Massey Cancer Center, Department of Human and Molecular Genetics, VCU Institute of Molecular Medicine (VIMM), Virginia Commonwealth University, Richmond, VA 23298, USA.
Cancers (Basel). 2021 Apr 9;13(8):1792. doi: 10.3390/cancers13081792.
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.
癌症的发生源于癌细胞自身获得大量遗传和表观遗传改变,以及其微环境的持续变化。癌细胞的可塑性使它们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性压力。对治疗的抗性,无论是固有抗性还是治疗开始后获得的抗性,都是肿瘤学家在有效管理该疾病过程中面临的主要障碍。对化疗的抗性,即化学抗性,是侵袭性癌症的一个重要标志,驱动癌基因诱导的信号通路和分子异常为化学抗性创造了平台。癌基因星形胶质细胞上调基因-1/黏附素(AEG-1/MTDH)在多种癌症中过表达,其过表达促进癌症的所有特征,如增殖、侵袭、转移、血管生成和化学抗性。本综述全面描述了AEG-1促进肿瘤发生的分子机制,特别强调了其调节化学抗性的能力。