Merkel Cell Polyomavirus: Oncogenesis in a Stable Genome.

Merkel Cell Polyomavirus: Oncogenesis in a Stable Genome.
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默克尔细胞多瘤病毒:稳定基因组中的肿瘤发生。

DOI:
10.3390/v14010058
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发表时间:
2021-12-30
期刊:
Viruses
影响因子:
--
通讯作者:
DeCaprio JA
DeCaprio JA
中科院分区:
其他
文献类型:
--
作者:
Ahmed MM;Cushman CH;DeCaprio JA

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默克尔细胞多瘤病毒(MCV)是大多数默克尔细胞癌(MCC)病例的病原体。多瘤病毒相关MCC(MCCP)的特征在于MCV DNA整合到肿瘤基因组中和低肿瘤突变负荷。相比之下,非病毒MCC(MCCN)的特征在于由UV损伤诱导的高肿瘤突变负荷。自从发现MCV以来,该领域的许多工作都集中在理解由MCV肿瘤(T)抗原驱动的肿瘤发生的分子机制上。在这里,我们回顾了我们目前的理解,大T(LT)和小T(ST)的活动如何促进MCC肿瘤发生的基因组不稳定性的情况下。我们强调LT和ST如何抑制肿瘤抑制因子以逃避生长抑制,这是一个重要的癌症标志。我们讨论ST与细胞蛋白的相互作用,重点是那些有助于维持增殖信号。最后,我们研究了活跃的研究领域,包括MCC的起源和病毒整合的机制。
Merkel cell polyomavirus (MCV) is the causative agent for the majority of Merkel cell carcinoma (MCC) cases. Polyomavirus-associated MCC (MCCP) is characterized by the integration of MCV DNA into the tumor genome and a low tumor mutational burden. In contrast, nonviral MCC (MCCN) is characterized by a high tumor mutational burden induced by UV damage. Since the discovery of MCV, much work in the field has focused on understanding the molecular mechanisms of oncogenesis driven by the MCV tumor (T) antigens. Here, we review our current understanding of how the activities of large T (LT) and small T (ST) promote MCC oncogenesis in the absence of genomic instability. We highlight how both LT and ST inhibit tumor suppressors to evade growth suppression, an important cancer hallmark. We discuss ST interactions with cellular proteins, with an emphasis on those that contribute to sustaining proliferative signaling. Finally, we examine active areas of research into open questions in the field, including the origin of MCC and mechanisms of viral integration.
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