LZTS2负向调控PI3K/AKT信号通路参与鼻咽癌放疗抵抗

鼻咽癌是头颈部最常见的恶性肿瘤之一，放疗抵抗是导致其局部区域复发的重要因素。研究发现LZTS2是一个潜在的抑癌基因，但其是否参与鼻咽癌放疗抵抗目前尚未有报道。本研究前期实验发现LZTS2可与PI3K的调节亚基p85相互结合，并负向调控PI3K/AKT的激活。由于PI3K/AKT信号通路在鼻咽癌细胞中高度活化，并与肿瘤放疗敏感性密切相关，我们推测：LZTS2通过与p85结合，促使p85入核，导致胞浆中p85与催化亚基p110的结合减少，从而抑制PI3K-AKT信号通路的激活，并最终增加鼻咽癌放疗敏感性。本研究将进一步阐明LZTS2负向调控PI3K/AKT信号通路的机制，以期明确LZTS2在鼻咽癌放疗抵抗中的作用，为鼻咽癌放射治疗增敏提供新的分子靶点，具有重要的理论价值与临床意义。

Radioresistance is a key factor involved in local and regional recurrence of nasopharyngeal carcinoma after treatment. It has been reported that LZTS2 is a candidate tumor suppressor gene. However, whether LZTS2 regulates radioresistance of nasopharyngeal cancer cells remains unknown. Our preliminary data show that LZTS2 can bind to p85, which is a regulatory subunit of PI3K, and negatively control the activation of PI3K/AKT signaling pathway. As PI3K/AKT pathway is highly activated in nasopharyngeal cancer cells and related to tumor radioresistance, we propose that LZTS2 competes with p110 for p85 binding, which leads to increased nucleus localization of p85, ultimately decreases radioresistance of nasopharyngeal cancer cells by inhibiting the PI3K/AKT signaling pathway. Therefore, this project intends to uncover the mechanism of how LZTS2 negatively controls the PI3K/AKT pathway, and explore the role of LZTS2 in radioresistance of nasopharyngeal cancer. This study will provide a novel molecular target for radiosensitization of nasopharyngeal cancer.