{"title":"人透明细胞肾细胞癌断路器癌进化模型的建立。","authors":"James J Hsieh, Emily H Cheng","doi":"10.15698/cst2020.08.227","DOIUrl":null,"url":null,"abstract":"<p><p>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 20<sup>th</sup> 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.</p>","PeriodicalId":36371,"journal":{"name":"Cell Stress","volume":null,"pages":null},"PeriodicalIF":4.1000,"publicationDate":"2020-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7380452/pdf/","citationCount":"2","resultStr":"{\"title\":\"Exploiting the circuit breaker cancer evolution model in human clear cell renal cell carcinoma.\",\"authors\":\"James J Hsieh, Emily H Cheng\",\"doi\":\"10.15698/cst2020.08.227\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>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 20<sup>th</sup> 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.</p>\",\"PeriodicalId\":36371,\"journal\":{\"name\":\"Cell Stress\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":4.1000,\"publicationDate\":\"2020-06-25\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7380452/pdf/\",\"citationCount\":\"2\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Cell Stress\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.15698/cst2020.08.227\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"CELL BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cell Stress","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.15698/cst2020.08.227","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
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.
Cell StressBiochemistry, 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.