Matsuda Satoru, Murakami Mutsumi, Ikeda Yuka, Nakagawa Yukie, Tsuji Ai, Kitagishi Yasuko
Department of Food Science and Nutrition, Nara Women's University, Nara 630-8506, Japan.
Biomed Rep. 2020 Sep;13(3):10. doi: 10.3892/br.2020.1317. Epub 2020 Jun 17.
Genomic perturbations due to inaccurate DNA replication, including inappropriate chromosomal segregation often underlie the development of cancer and neurodegenerative diseases. The incidence of these two diseases increases with age and exhibits an inverse association. Therefore, elderly subjects with cancer exhibit a reduced risk of a neurodegenerative disease, and vice versa. Both of these diseases are associated with aging and share several risk factors. Cells have multiple mechanisms to repair DNA damage and inaccurate replication. Previous studies have demonstrated that tumor suppressor proteins serve a critical role in the DNA damage response, which may result in genomic instability and thus induction of cellular apoptosis. Tumor suppressor genes, such as phosphatase and tensin homologue deleted on chromosome 10 , breast cancer susceptibility gene 1 ( and reduce genomic susceptibility to cancer by repairing the damaged DNA. In addition, these genes work cooperatively to ensure the inhibition of the development of several types of cancer. , and have been recognized as the most frequently deleted and/or mutated genes in various types of human cancer. Recently, tumor suppressor genes have also been shown to be involved in the development of neurodegenerative diseases. The present review summarizes the recent findings of the functions of these tumor suppressors that are associated with genomic stability, and are involved in carcinogenic and neurodegenerative cell signaling. A summary is presented regarding the interactions of these tumor suppressors with their partners which results in transduction of downstream signals. The implications of these functions for cancer and neurodegenerative disease-associated biology are also highlighted.
由于DNA复制不准确导致的基因组扰动，包括不适当的染色体分离，往往是癌症和神经退行性疾病发生发展的基础。这两种疾病的发病率均随年龄增长而增加，且呈负相关。因此，患癌症的老年受试者患神经退行性疾病的风险降低，反之亦然。这两种疾病都与衰老相关，且有若干共同的风险因素。细胞具有多种机制来修复DNA损伤和不准确的复制。先前的研究表明，肿瘤抑制蛋白在DNA损伤反应中起关键作用，这可能导致基因组不稳定，进而诱导细胞凋亡。肿瘤抑制基因，如10号染色体上缺失的磷酸酶和张力蛋白同源物、乳腺癌易感基因1（以及通过修复受损DNA降低基因组对癌症的易感性。此外，这些基因协同作用以确保抑制多种类型癌症的发生发展。 、 和 已被认为是各类人类癌症中最常发生缺失和/或突变的基因。最近，肿瘤抑制基因也被证明与神经退行性疾病的发生发展有关。本综述总结了这些与基因组稳定性相关、参与致癌和神经退行性细胞信号传导的肿瘤抑制因子功能的最新研究结果。还总结了这些肿瘤抑制因子与其伙伴的相互作用，这些相互作用导致下游信号的转导。这些功能对癌症和神经退行性疾病相关生物学的意义也得到了强调。
