Evolution of higher mesenchymal CD44 expression in the human lineage: A gene linked to cancer malignancy.
Evolution of higher mesenchymal CD44 expression in the human lineage: A gene linked to cancer malignancy.
复制标题
DOI：
10.1093/emph/eoac036
复制
发表时间：
2022
影响因子：
3.7
通讯作者：
Wagner, Gunter P.
中科院分区：
文献类型：
--
作者：
Ma, Xinghong;Dighe, Anasuya;Maziarz, Jamie;Neumann, Edwin;Erkenbrack, Eric;Hei, Yuan-Yuan;Liu, Yansheng;Suhail, Yasir;Kshitiz;Pak, Irene;Levchenko, Andre;Wagner, Gunter P.
CD44 是一种与癌症进展有关的细胞外基质受体。 CD44 增加癌症和滋养层细胞对皮肤 (SF) 和子宫内膜基质成纤维细胞 (ESF) 的侵袭。我们推断，CD44 表达的进化可以影响 ESF 中通过 CD44 进行的胎儿-母体相互作用，以及通过 SF 中的表达影响罹患恶性肿瘤的脆弱性。我们研究了哺乳动物 SF 和 ESF 中 CD44 表达的进化，并证明人类谱系中进化出了更高的 CD44 表达。牛和人体内的同工型表达非常相似，表明侵袭性的差异并不是由于表达的同工型的性质造成的。然后我们询问两种细胞类型中基因表达的协同增加是否是由于共同的调控机制或由于细胞类型特异性因素所致。对人和牛的细胞和顺式调控元件进行的报告基因实验表明，CD44 表达的差异是由于顺式效应以及细胞类型特异性反式效应造成的。这些结果表明，协同表达增加可能是由于选择作用于两种细胞类型，因为细胞类型特异性因子的进化变化需要对细胞类型特异性功能的选择。这种情况意味着人类中 CD44 表达升高的恶性增强效应可能是由于 CD44 的其他尚未识别的功能的正选择的副作用而进化的。一个可能的候选者是 CD44 的抗纤维化作用，但没有可靠的数据表明人类和灵长类动物的纤维化程度低于其他哺乳动物。
CD44 is an extracellular matrix receptor implicated in cancer progression. CD44 increases the invasibility of skin (SF) and endometrial stromal fibroblasts (ESF) by cancer and trophoblast cells. We reasoned that the evolution of CD44 expression can affect both, the fetal–maternal interaction through CD44 in ESF as well as vulnerability to malignant cancer through expression in SF. We studied the evolution of CD44 expression in mammalian SF and ESF and demonstrate that in the human lineage evolved higher CD44 expression. Isoform expression in cattle and human is very similar suggesting that differences in invasibility are not due to the nature of expressed isoforms. We then asked whether the concerted gene expression increase in both cell types is due to shared regulatory mechanisms or due to cell type-specific factors. Reporter gene experiments with cells and cis-regulatory elements from human and cattle show that the difference of CD44 expression is due to cis effects as well as cell type-specific trans effects. These results suggest that the concerted expression increase is likely due to selection acting on both cell types because the evolutionary change in cell type-specific factors requires selection on cell type-specific functions. This scenario implies that the malignancy enhancing effects of elevated CD44 expression in humans likely evolved as a side-effect of positive selection on a yet unidentified other function of CD44. A possible candidate is the anti-fibrotic effect of CD44 but there are no reliable data showing that humans and primates are less fibrotic than other mammals.
登录
查看更多内容
DOI：
10.1093/bioinformatics/btr064
发表时间：
2011-04-01
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Grant CE;Bailey TL;Noble WS
通讯作者：
Noble WS
DOI：
10.1126/science.1260793
发表时间：
2015-02-06
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Battle A;Khan Z;Wang SH;Mitrano A;Ford MJ;Pritchard JK;Gilad Y
通讯作者：
Gilad Y
DOI：
10.1007/978-1-59745-243-4_12
发表时间：
2009
期刊：
Methods in molecular biology (Clifton, N.J.)
影响因子：
--
作者：
Li, Huai;Sun, Yu;Zhan, Ming
通讯作者：
Zhan, Ming
影响因子：
14.9
作者：
Khan A;Fornes O;Stigliani A;Gheorghe M;Castro-Mondragon JA;van der Lee R;Bessy A;Chèneby J;Kulkarni SR;Tan G;Baranasic D;Arenillas DJ;Sandelin A;Vandepoele K;Lenhard B;Ballester B;Wasserman WW;Parcy F;Mathelier A
通讯作者：
Mathelier A
DOI：
10.1074/mcp.ra117.000314
发表时间：
2017-12
期刊：
Molecular & cellular proteomics : MCP
影响因子：
--
作者：
Bruderer R;Bernhardt OM;Gandhi T;Xuan Y;Sondermann J;Schmidt M;Gomez-Varela D;Reiter L
通讯作者：
Reiter L