The Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai JiaoTong University School of Medicine, Shanghai, China.
Thorac Cancer. 2011 Nov;2(4):143-148. doi: 10.1111/j.1759-7714.2011.00064.x.
We and others recently identified the gene metadherin (MTDH) as a functional driver in multiple aspects of cancer progression. It is overexpressed in cancer cells originating from a variety of tissues, partially due to DNA amplification of the chromosomal 8q22 region where this gene resides. The rapidly accumulated data from MTDH studies of the past several years have documented its role in tumorigenesis, angiogenesis, cell proliferation, survival, anchorage-independent growth, metastasis and chemoresistance. In particular, it simultaneously helps the primary tumor cells to survive conventional chemotherapy and spread to distant organs, both of which are major contributors to cancer therapy failure and ultimately patient death. The efforts to elucidate the molecular mechanism of MTDH functions led to observations indicating its involvement in several prominent cancer-related signaling pathways including Ras, c-Myc, PI3K/AKT, NF-κB, Wnt/β-catenin, and more recently, microRNA machinery. Herein we will briefly summarize the studies that establish MTDH as a promising target for cancer therapeutics.
我们和其他人最近确定了基因 MTDH(多梳抑制物 1)作为癌症进展多个方面的功能驱动基因。它在源自多种组织的癌细胞中过度表达,部分原因是该基因所在的染色体 8q22 区域的 DNA 扩增。过去几年中关于 MTDH 研究的快速积累数据记录了它在肿瘤发生、血管生成、细胞增殖、存活、无锚定生长、转移和化疗耐药性中的作用。特别是,它同时帮助原发性肿瘤细胞耐受常规化疗并扩散到远处器官,这两者都是癌症治疗失败并最终导致患者死亡的主要原因。阐明 MTDH 功能的分子机制的努力导致了一些观察结果,表明它参与了包括 Ras、c-Myc、PI3K/AKT、NF-κB、Wnt/β-catenin 在内的几个突出的癌症相关信号通路,以及最近的 microRNA 机制。在此,我们将简要总结确立 MTDH 作为癌症治疗有前途的靶标的研究。