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CDK20 在有丝分裂内外:血液系统恶性肿瘤的预后因素和治疗靶点。

CDC20 in and out of mitosis: a prognostic factor and therapeutic target in hematological malignancies.

机构信息

Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna and Institute of Hematology "L. e A. Seràgnoli", Bologna, Italy.

Biosciences Laboratory, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori", via Piero Maroncelli 40, 47014, Meldola, FC, Italy.

出版信息

J Exp Clin Cancer Res. 2022 Apr 30;41(1):159. doi: 10.1186/s13046-022-02363-9.

Abstract

Cell division cycle 20 homologue (CDC20) is a well-known regulator of cell cycle, as it controls the correct segregation of chromosomes during mitosis. Many studies have focused on the biological role of CDC20 in cancer development, as alterations of its functionality have been linked to genomic instability and evidence demonstrated that high CDC20 expression levels are associated with poor overall survival in solid cancers. More recently, novel CDC20 functions have been demonstrated or suggested, including the regulation of apoptosis and stemness properties and a correlation with immune cell infiltration. Here, we here summarize and discuss the role of CDC20 inside and outside mitosis, starting from its network of interacting proteins. In the last years, CDC20 has also attracted more interest in the blood cancer field, being overexpressed and showing an association with prognosis both in myeloid and lymphoid malignancies. Preclinical findings showed that selective CDC20 and APC/C/APC/C inhibitors, namely Apcin and proTAME, are effective against lymphoma and multiple myeloma cells, resulting in mitotic arrest and apoptosis and synergizing with clinically-relevant drugs. The evidence and hypothesis presented in this review provide the input for further biological and chemical studies aiming to dissect novel potential CDC20 roles and targeting strategies in hematological malignancies.

摘要

细胞分裂周期 20 同源物(CDC20)是细胞周期的著名调节剂,因为它控制有丝分裂过程中染色体的正确分离。许多研究都集中在 CDC20 在癌症发展中的生物学作用上,因为其功能的改变与基因组不稳定性有关,并且有证据表明,在实体癌中,CDC20 的高表达水平与总体生存率差有关。最近,已经证明或提出了 CDC20 的新功能,包括对细胞凋亡和干性特性的调节,以及与免疫细胞浸润的相关性。在这里,我们从其相互作用蛋白网络开始,总结和讨论了 CDC20 在有丝分裂内外的作用。在过去的几年中,CDC20 在血液癌领域也引起了更多的关注,在髓系和淋巴恶性肿瘤中均过度表达,并与预后相关。临床前研究结果表明,选择性 CDC20 和 APC/C/APC/C 抑制剂,即 Apcin 和 proTAME,对淋巴瘤和多发性骨髓瘤细胞有效,导致有丝分裂停滞和凋亡,并与临床相关药物具有协同作用。本综述中提出的证据和假设为进一步的生物学和化学研究提供了依据,旨在剖析血液恶性肿瘤中 CDC20 的新潜在作用和靶向策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/601d/9055704/2f94c826ddc7/13046_2022_2363_Fig1_HTML.jpg

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