Department of Biological & Environmental Sciences, College of Arts and Science, Qatar University, Doha, Qatar.
College of Medicine, QU Health, Qatar University, Doha, Qatar.
J Cell Mol Med. 2021 Mar;25(5):2309-2314. doi: 10.1111/jcmm.16296. Epub 2021 Jan 24.
Using a validated tetracycline-off-inducible CD44 expression system in mouse model, we have previously demonstrated that the hyaluronan (HA) receptor CD44 promotes breast cancer (BC) metastasis to the liver. To unravel the mechanisms that underpin CD44-promoted BC cell invasion, RNA samples were isolated from two cell models: (a) a tetracycline (Tet)-Off-regulated expression system of the CD44s in MCF-7 cells and; (b) as a complementary approach, the highly metastatic BC cells, MDA-MB-231, were cultured in the presence and absence of 50 µg/mL of HA. Kynureninase (KYNU), identified by Microarray analysis, was up-regulated by 3-fold upon induction and activation of CD44 by HA; this finding suggests that KYNU is a potential novel transcriptional target of CD44-downtstream signalling. KYNU is a pyridoxal phosphate (PLP) dependent enzyme involved in the biosynthesis of NAD cofactors from tryptophan that has been associated with the onset and development of BC. This review will attempt to identify and discuss the findings supporting this hypothesis and the mechanisms linking KYNU cell invasion via CD44.
使用在小鼠模型中验证的四环素诱导型 CD44 表达系统，我们之前已经证明透明质酸（HA）受体 CD44 促进乳腺癌（BC）转移到肝脏。为了揭示支持 CD44 促进 BC 细胞侵袭的机制，我们从两个细胞模型中分离 RNA 样本：（a）MCF-7 细胞中四环素（Tet）调控的 CD44s 表达系统；和（b）作为互补方法，高转移性 BC 细胞 MDA-MB-231 在存在和不存在 50µg/mLHA 的情况下培养。通过微阵列分析鉴定的犬尿氨酸酶（KYNU）在 HA 诱导和激活 CD44 时上调 3 倍；这一发现表明 KYNU 是 CD44 下游信号传导的潜在新型转录靶标。KYNU 是一种依赖吡哆醛磷酸（PLP）的酶，参与色氨酸合成 NAD 辅因子，与 BC 的发生和发展有关。本综述将尝试确定和讨论支持这一假设的发现，以及通过 CD44 连接 KYNU 细胞侵袭的机制。
