根據(jù)2月發(fā)表于《癌細胞》（Cancer Cell）中的一項新研究顯示,，細胞內(nèi)訊息傳導(dǎo)機制中MAPK路徑的p38-alpha,，能夠偵測細胞內(nèi)的氧化壓力的變化,，能夠進一步抑制腫瘤的生長,。
p38是訊息傳遞路徑MAPK中的一個激酶,，先前研究已知其參與細胞內(nèi)壓力的調(diào)控,，包括氧自由基的一種活性氧（reactive oxygen species,，ROS）,。西班牙國家癌癥中心的Angel R. Nebreda博士與其研究團隊利用缺乏p38-alpha的突變實驗鼠，證實了p38-alpha在腫瘤生理學(xué)上扮演了抑制癌細胞的重要角色,。
研究者表示,，致癌基因（oncogene）活化造成ROS上升，細胞隨即透過p38-alpha啟動細胞凋亡（apoptosis）來阻止癌化,；但他們亦發(fā)現(xiàn),，致癌基因似乎能夠反過來調(diào)控ROS的量來“躲避”這項保護機制。
專家表示,，這項結(jié)果不僅有助于控制癌細胞的發(fā)展,，也為新式抗癌治療法的研發(fā)提供許多有力的參考。
部分英文原文：
p38α MAP Kinase as a Sensor of Reactive Oxygen Species in Tumorigenesis
Ignacio Dolado,1,2 Aneta Swat,1 Nuria Ajenjo,1 Gabriella De Vita,3 Ana Cuadrado,1 and Angel R. Nebreda1,
1 CNIO (Spanish National Cancer Center), Melchor Fernández Almagro 3, 28029 Madrid, Spain
2 EMBL, Meyerhofstrasse 1, 69117 Heidelberg, Germany
3 CEINGE, Via Comunale Margherita 482, 80131 Naples, Italy
Corresponding author
Angel R. Nebreda
[email protected]
Summary
p38α is a stress-activated protein kinase that negatively regulates malignant transformation induced by oncogenic H-Ras, although the mechanisms involved are not fully understood. Here, we show that p38α is not a general inhibitor of oncogenic signaling, but that it specifically modulates transformation induced by oncogenes that produce reactive oxygen species (ROS). This inhibitory effect is due to the ROS-induced activation of p38α early in the process of transformation, which induces apoptosis and prevents the accumulation of ROS and their carcinogenic effects. Accordingly, highly tumorigenic cancer cell lines have developed a mechanism to uncouple p38α activation from ROS production. Our results indicate that oxidative stress sensing plays a key role in the inhibition of tumor initiation by p38α.
