Leptin-PDK1-SGK1信号轴在肾癌-脂肪微环境中促进肿瘤恶性演进的机制研究

Renal cell carcinoma (RCC) is one of most common malignancies of the urinary system. Relapse and metastasis of patients with high-risk local RCC after surgery is a vexing problem in the clinic and predominately associated with poor survival. Unfortunately, the exact molecular mechanism underlying RCC relapse and metastasis are not well understood. Recently, increasing studies have begun to focus on the role of adipocytes in tumor progression and demonstrated the pivotal role of tumor-adipocyte associated microenvironment in tumor progression. However, almost nothing is known for the role of adipocytes in RCC progression. In our previously study, the rapid progression of RCC cells seems to be driven by a novel Leptin-PDK1-SGK1 axis within tumor-adipocyte microenvironment. Based on these results mentioned above, we are planning to confirm the role of this crucial signaling in RCC recurrence and metastasis, and further illuminate the exact mechanism by using diverse methods and techniques. Therefore, Leptin-PDK1-SGK1 axis would be expected to be a promising targets for reducing recurrence and metastasis in patients with RCC.

肾癌是泌尿系统常见的恶性肿瘤之一。高危局限性肾癌根治术后肿瘤易复发、转移，是临床面临的棘手问题，亦是影响患者预后的重要因素。目前，对于肾癌复发、转移的分子机制研究欠清晰。最近研究发现，肿瘤微环境中的脂肪细胞是导致肿瘤复发和转移的重要因素，但肾癌-脂肪细胞的相互作用是否参与肿瘤恶性生物学进程，目前仍不清楚。结合国外相关研究，本课题前期通过iTRAQ、RNA-seq和Luminex多因子检测等研究提示：肾癌-脂肪细胞间可能通过Leptin-PDK1-SGK1信号通路启动肾癌细胞的快速演进。本课题拟运用多种实验技术，证实Leptin-PDK1-SGK1信号轴是导致肾癌复发和转移的重要信号通路，并阐明该信号通路介导肿瘤细胞增殖和转移的具体分子机制，最终可能为控制肾癌复发和转移提供新思路。

肾癌是泌尿系统常见的恶性肿瘤之一。高危局限性肾癌根治术后肿瘤易复发、转移，是临床面临的棘手问题，亦是影响患者预后的重要因素。目前，对于肾癌复发、转移的分子机制研究欠清晰。最近研究发现，肿瘤微环境中的脂肪细胞是导致肿瘤复发和转移的重要因素，但肾癌-脂肪细胞的相互作用是否参与肿瘤恶性生物学进程，目前仍不清楚。本课题通过多种技术手段结合体内、外研究证实：肾癌-脂肪细胞间可能通过Leptin-PDK1-SGK1信号通路诱导肾癌细胞的早期复发和快速演进。脂肪细胞来源的Leptin通过激活PDK1，活化SGK1及其下游的转录因子介导肿瘤的上皮间质转化，最终诱导肿瘤早期复发和快速演进。本研究证实Leptin-PDK1-SGK1信号轴是导致肾癌复发和转移的重要信号通路，并阐明该信号通路介导肿瘤细胞增殖和转移的具体分子机制，最终可能为控制肾癌复发和转移提供新思路。