极性基因 Scribble是一种抑癌基因，极性基因异常在肿瘤中的重要作用近年来受到很大关注，但认识还非常有限。我们预实验发现Scribble基因与非小细胞肺癌对顺铂敏感性密切相关。近年Tak Mak综述道ROS信号在决定肿瘤化学疗效中具有重要作用，顺铂等均可通过ROS起作用。而NOX家族是重要的ROS信号来源。我们初步的研究结果提示Scribble可与NOX家族核心蛋白p22phox结合，从而活化NOX亚基以及导致ROS信号蓄积，触发肿瘤细胞对顺铂发生凋亡，最终影响肿瘤细胞对化疗药物的敏感性；而回复Scribble水平显示其顺铂的敏感性明显上升。我们将探讨Scribble与NOX作用与Rac1活化的分子机制，以及Scribble在调控NOX蛋白泛素化降解的机制。并且探讨临床上Scribble作为肺癌化疗敏感性标志物以及预后指标的可能性，并为探索临床化疗敏感性提供新的治疗靶点。

Disruption of cell polarity is an important hallmark of cancer. A set of crucial polarity proteins are known as tumor suppressors based upon studies in Drosophila. The role polarity protein Scribble plays during tumorigenesis in mammals is still poorly understood. The appearance of cancer cell population loss sensitivity to chemotherapeutic agents represents a major problem in the treatment of cancer patients. The regulation of oxidative stress is an important factor in tumour responses to anticancer therapies. In fact, many antitumor agents, such as cisplatin, vinblastine, doxorubicin, camptothecin, neocarzinostatin and many others exhibit antitumor activity via ROS-dependent activation of apoptotic cell death, suggesting potential use of ROS as an antitumor principle. Thus, a unique anticancer strategy named "oxidation therapy" has been developed by inducing cytotoxic oxystress for cancer treatment. Drug resistance,the principal mechanism by which cancer develop resistance to chemotherapy drugs, is a major factor in the failure of chemotherapy. We generated several drug-resistant cancer cell lines, We demonstrated that downregulation of Scribble induced cisplatin-related drug resistance in those cells. This approach shows that decreased sensitivity to drug mediated by the loss of expression of Scribble, is one mechanism that tumor cells use to escape death induced by chemotherapeutic agents. However, the molecular mechanism by which Scribble regulates drug sensitivity to anti-cancer treatment has remained elusive. We showed that downregulation of Scribble conferred increased cisplatin resistance by blocking NOX-derived ROS signaling and apoptosis. This study will focuses on the pathologic role of the Scribble in lung cancer and on the potential therapeutic implication of targeting this axis for the treatment. we will demonstrated that Scribble binding to NADPH oxidase was critical for the generation of reactive oxygen species and cisplatin-induced apoptosis. . This work reveals a potential mechanism whereby polarity protein Scribble involves in redox signaling of cancer cells and impacts on redox-sensitive pathologies, such as resistance to apoptosis after treatment of NSCLC.Our study will enable us to predict the clinical effect of chemotherapy and, provides an effective and pivotal target for the development of new antitumor drugs.