根据2月发表于《癌细胞》（Cancer Cell）中的一项新研究显示，细胞内讯息传导机制中MAPK路径的p38-alpha，能够侦测细胞内的氧化压力的变化，能够进一步抑制肿瘤的生长。
p38是讯息传递路径MAPK中的一个激酶，先前研究已知其参与细胞内压力的调控，包括氧自由基的一种活性氧（reactive oxygen species，ROS）。西班牙国家癌症中心的Angel R. Nebreda博士与其研究团队利用缺乏p38-alpha的突变实验鼠，证实了p38-alpha在肿瘤生理学上扮演了抑制癌细胞的重要角色。
研究者表示，致癌基因（oncogene）活化造成ROS上升，细胞随即透过p38-alpha启动细胞凋亡（apoptosis）来阻止癌化；但他们亦发现，致癌基因似乎能够反过来调控ROS的量来“躲避”这项保护机制。
专家表示，这项结果不仅有助于控制癌细胞的发展，也为新式抗癌治疗法的研发提供许多有力的参考。
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
anebreda@cnio.es
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.
