Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, Italy.
Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, Italy; Advanced Technologies Network Center (ATEN Center), University of Palermo, Italy.
Life Sci. 2024 Aug 1;350:122788. doi: 10.1016/j.lfs.2024.122788. Epub 2024 Jun 5.
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.
凋亡抑制蛋白(IAPs)是通过旨在挽救昆虫细胞凋亡的实验发现的。IAP 成员 Survivin 与凋亡抑制经典相关,它还调节细胞周期进程,是染色体乘客复合物(CPC)的重要组成部分,负责染色体分离。虽然在大多数成年组织中无法检测到 Survivin,但它在成体干细胞(ASCs)中表达,并在其维持中发挥关键作用。Survivin 在大多数癌症中过度表达,促进其克隆扩增。因此,近二十年来,它被提议作为一种潜在的抗癌靶点。在本次讨论中,我们将探讨 Survivin 作为治疗靶点的基本原理,重点关注常见的癌症类型,如癌、肉瘤和白血病。我们将深入研究 Survivin 被癌症促进生存的细胞信号转导调节,SNP 与肿瘤发生之间的关联,以及 miRNA 对其的调节。最后,我们将比较细胞生长、集落形成能力和凋亡,以及 Survivin 抑制的不同策略,包括基因表达和蛋白活性调节。