Ahmad Salma M S, Al-Mansoob Maryam, Ouhtit Allal
Biological Sciences Program, Department of Biological & Environmental Sciences, College of Arts and Science, Qatar University, Doha, Qatar.
Front Oncol. 2022 Nov 23;12:1038121. doi: 10.3389/fonc.2022.1038121. eCollection 2022.
Our tetracycline-off-inducible CD44 expression system previously established in mouse model, revealed that activation of CD44 with its major ligand hyaluronan (HA) promoted breast cancer (BC) metastasis to the liver. To identify the mechanisms that underpin CD44-promoted BC cell invasion, microarray gene expression profiling using RNA samples from (Tet)-Off-regulated expression system of CD44s in MCF7 cells, revealed a set of upregulated genes including, nuclear sirtuin-1 ( also known as NAD-dependent deacetylase), an enzyme that requires NAD as a cofactor to deacetylate several histones and transcription factors. It stimulates various oncogenic pathways promoting tumorigenesis. This data suggests that is a potential novel transcriptional target of CD44-downstream signaling that promote BC cell invasion/metastasis. This review will discuss the evidence supporting this hypothesis as well as the mechanisms linking to cell proliferation and invasion.
我们先前在小鼠模型中建立的四环素诱导型CD44表达系统显示，CD44与其主要配体透明质酸（HA）的激活促进了乳腺癌（BC）向肝脏的转移。为了确定支持CD44促进BC细胞侵袭的机制，使用来自MCF7细胞中CD44s的（Tet）-Off调控表达系统的RNA样本进行微阵列基因表达谱分析，发现了一组上调基因，包括核沉默调节蛋白-1（也称为NAD依赖性脱乙酰酶），一种需要NAD作为辅助因子来使几种组蛋白和转录因子脱乙酰化的酶。它刺激各种致癌途径促进肿瘤发生。该数据表明，是促进BC细胞侵袭/转移的CD44下游信号传导的潜在新型转录靶点。本综述将讨论支持这一假设的证据以及将与细胞增殖和侵袭联系起来的机制。
