肺癌是最常见且死亡率最高的恶性肿瘤之一。铁死亡Ferroptosis是新近发现的一种新型细胞死亡方式，是肿瘤治疗的潜在新靶点，但铁死亡发生的机制尚不清楚。申请人前期研究发现，Rab蛋白负性调控因子TBC1D10B在肺腺癌中高表达与病人预后不良密切相关，并可使肿瘤细胞抵抗铁死亡。基于此，我们拟开展以下研究内容：1）探讨TBC1D10B在肺腺癌中异常高表达具有促癌的作用，揭示其发生高表达的转录调控机制；2）筛选并鉴定TBC1D10B的下游靶基因和相互作用蛋白。本项目将阐明TBC1D10与转铁蛋白受体TfR-1通路调控肺腺癌细胞铁代谢与铁死亡的分子机制，为肺腺癌的治疗提供新的靶点和科学依据。

Lung carcinoma is one of the cancers with the highest incidence and mortality. Ferroptosis has recently been discovered as a new method of cell death, and notably it is a potential target for cancer therapy. Nevertheless, the mechanism of Ferroptosis remains unknown. We have previously revealed that high expression level of Rab negative regulator, namely TBC1D10B, in lung adenocarcinoma is closely related to poor prognosis of patients, and it makes tumor cells resistant to Ferroptosis. Based upon these findings, we will conduct the following studies: i) to probe the cancer promotion effect of highly expressed TBC1D10B in lung adenocarcinoma and to uncover its transcriptional activation mechanism ; ii) to screen and identify the downstream target genes and interacting proteins of TBC1D10B. This study will elucidate the molecular mechanism by which TBC1D10B and transferrin receptor TfR-1 pathway regulates iron metabolism and inhibits Ferroptosis, which could provide novel targets and scientific basis for treating lung adenocarcinoma.