Abstract:
Inhibitors of Apoptosis proteins (IAPs) were discovered through experiments aimed at rescuing apoptosis in insects. Classically associated with the inhibition of apoptosis, the IAP member Survivin also regulates cell cycle progression and is an essential component of the Chromosomal Passenger Complex (CPC), responsible for chromosomal segregation. Although undetectable in most adult tissues, Survivin is expressed in Adult Stem Cells (ASCs) and plays a crucial role in their maintenance. Survivin is overexpressed in most cancers, contributing to their clonal expansion. As a result, it has been proposed as a possible anticancer target for nearly two decades. In this discussion, we will explore the rationale behind Survivin as a therapeutic target, focusing on common cancer types such as carcinomas, sarcomas, and leukemias. We will delve into the modulation of Survivin by cancer pro-survival cell signaling, the association between SNPs and tumorigenesis, and its regulation by miRNAs. Finally, we will compare cell growth, clonogenic capacity, and apoptosis, along with different strategies for Survivin inhibition, including gene expression and protein activity modulation.
摘要:
通过旨在挽救昆虫凋亡的实验发现了凋亡蛋白(IAP)的抑制剂。与细胞凋亡的抑制经典相关,IAP成员Survivin还调节细胞周期进程,并且是染色体过客复合物(CPC)的重要组成部分,负责染色体分离。虽然在大多数成人组织中检测不到,Survivin在成体干细胞(ASC)中表达,并在其维持中起着至关重要的作用。Survivin在大多数癌症中过度表达,有助于他们的克隆扩张。因此,近二十年来,它一直被认为是一种可能的抗癌靶标。在这次讨论中,我们将探索Survivin作为治疗靶点背后的基本原理,专注于常见的癌症类型,如癌,肉瘤,和白血病。我们将深入研究癌症前存活细胞信号传导对Survivin的调节,SNP和肿瘤发生之间的关联,及其通过miRNA的调控。最后,我们将比较细胞生长,克隆能力,和细胞凋亡,以及不同的生存素抑制策略,包括基因表达和蛋白质活性调节。