人透明细胞肾细胞癌断路器癌进化模型的建立。

IF 4.1 Q2 CELL BIOLOGY
James J Hsieh, Emily H Cheng
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引用次数: 2

摘要

易感人群与其各自的宏观/微观环境之间的持续相互作用贯穿其一生,导致个体癌症的最终表现。20世纪初以来,随着人类平均寿命超过50岁,衰老这一“时间”因素与宿主和环境因素一起在癌症发病率中发挥着越来越大的作用。癌症是一种由于致癌基因(癌基因;OG)和/或肿瘤抑制基因(肿瘤抑制基因;次数)。除了它们与癌症的整体关系外,事实上,像人类这样的高等生物需要及时部署特定的OG和/或TSG来应对各自的生理和病理状况。在过去的十年中,广泛的人类肾癌基因组学已经完成,并且已经产生了概括人类肾癌病理生物学的新型小鼠模型。通过研究透明细胞肾细胞癌(ccRCC)(最常见的肾癌类型)积累的新的基因组学、遗传学、机制、临床和治疗方面的见解,我们设想了一个基于OG-TSG信号对的癌症进化模型,类似于断路器(CB),允许必要的信号输出,同时防止有害的信号过度驱动。因此,这一观点旨在提供一个循序渐进的机制解释/说明,说明固有的OG-TSG CBs如何复杂地协同作用于生物体的健康;以及体细胞突变(遗传适应性的重要组成部分)如何在不经意间引发特定的CBs序列中断,而这些CBs通常起着维持和保护个体组织稳态的作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Exploiting the circuit breaker cancer evolution model in human clear cell renal cell carcinoma.

Exploiting the circuit breaker cancer evolution model in human clear cell renal cell carcinoma.

Exploiting the circuit breaker cancer evolution model in human clear cell renal cell carcinoma.

The incessant interactions between susceptible humans and their respective macro/microenvironments registered throughout their lifetime result in the ultimate manifestation of individual cancers. With the average lifespan exceeding 50 years of age in humans since the beginning of 20th century, aging - the "time" factor - has played an ever-increasing role alongside host and environmental factors in cancer incidences. Cancer is a genetic/epigenetic disease due to gain-of-function mutations in cancer-causing genes (oncogene; OG) and/or loss-of-function mutations in tumor-suppressing genes (tumor suppressor genes; TSG). In addition to their integral relationship with cancer, a timely deployment of specific OG and/or TSG is in fact needed for higher organisms like human to cope with respective physiological and pathological conditions. Over the past decade, extensive human kidney cancer genomics have been performed and novel mouse models recapitulating human kidney cancer pathobiology have been generated. With new genomic, genetic, mechanistic, clinical and therapeutic insights accumulated from studying clear cell renal cell carcinoma (ccRCC)-the most common type of kidney cancer, we conceived a cancer evolution model built upon the OG-TSG signaling pair analogous to the electrical circuit breaker (CB) that permits necessary signaling output and at the same time prevent detrimental signaling overdrive. Hence, this viewpoint aims at providing a step-by-step mechanistic explanation/illustration concerning how inherent OG-TSG CBs intricately operate in concert for the organism's wellbeing; and how somatic mutations, the essential component for genetic adaptability, inadvertently triggers a sequential outage of specific sets of CBs that normally function to maintain and protect and individual tissue homeostasis.

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来源期刊
Cell Stress
Cell Stress Biochemistry, Genetics and Molecular Biology-Biochemistry, Genetics and Molecular Biology (miscellaneous)
CiteScore
13.50
自引率
0.00%
发文量
21
审稿时长
15 weeks
期刊介绍: Cell Stress is an open-access, peer-reviewed journal that is dedicated to publishing highly relevant research in the field of cellular pathology. The journal focuses on advancing our understanding of the molecular, mechanistic, phenotypic, and other critical aspects that underpin cellular dysfunction and disease. It specifically aims to foster cell biology research that is applicable to a range of significant human diseases, including neurodegenerative disorders, myopathies, mitochondriopathies, infectious diseases, cancer, and pathological aging. The scope of Cell Stress is broad, welcoming submissions that represent a spectrum of research from fundamental to translational and clinical studies. The journal is a valuable resource for scientists, educators, and policymakers worldwide, as well as for any individual with an interest in cellular pathology. It serves as a platform for the dissemination of research findings that are instrumental in the investigation, classification, diagnosis, and therapeutic management of major diseases. By being open-access, Cell Stress ensures that its content is freely available to a global audience, thereby promoting international scientific collaboration and accelerating the exchange of knowledge within the research community.
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