乏氧微环境是包括肺癌在内的实体肿瘤的一个基本特性。肿瘤在乏氧环境下，通过调控下游基因及信号通路，促使肿瘤凋亡途径的失活，引起肿瘤进展。AHNAK2是AHNAK家族的新成员，AHNAK在肿瘤的发展中起到重要作用，而关于AHNAk2的肿瘤研究鲜有报道。我们前期发掘TCGA数据库，发现AHNAK2基因在非小细胞肺癌中过表达且其表达水平与预后呈负相关；细胞实验揭示AHNAK2在非小细胞肺癌的抗凋亡过程中起到了重要作用。我们进一步发现乏氧诱导因子1能显著地促进AHNAK2的表达，因此我们推测AHNAK2可能是乏氧微环境下肿瘤抗凋亡的关键分子。我们拟阐明AHNAK2在非小细胞肺癌中的表达方式及其临床意义；拟以HIF1调控AHNAK2的表达为切入点，从组织水平、细胞水平和动物模型三个层面，阐明乏氧环境下AHNAK2在非小细胞肺癌抗凋亡过程中的作用及其调控机制，为挖掘新的肺癌治疗靶点提供理论依据。

Hypoxic microenvironment is a basic characteristic of solid tumors, including lung cancer. By regulating the downstream genes and signalling pathways, the hypoxic tumor environment prompts the inactivation of tumor apoptosis pathway and causes tumor progression. AHNAK2 is a new member of the AHNAK family. AHNAK plays important roles in tumor development and tumor progression, however, the role of AHNAk2 in tumor progression was seldomly reported. In the preliminary work we explored the TCGA database and found that AHNAK2 gene was abnormally expressed in non-small cell lung cancer (NSCLC). The expression level of AHNAK2 was negatively correlated with the prognosis of patients with NSCLC. In vitro assays we found that the down-regulation of AHNAK2 lead to a significant increase of starvation-induced apoptosis in NSCLC cells. In addition we found that hypoxia-inducible factor-1 (HIF1) plays an essential role in promoting AHNAK2 expression. We here propose a scientific hypothesis that AHNAK2 may be a key anti-apoptotic molecule in tumor hypoxic microenvironment. In the present programe we intend to detect AHNAK2 expression in NSCLC tumor tissues and cell lines and then investigate its clinical significance. The mechanism how HIF-1 regulates AHNAK2 gene expression will be explored. We will try to clarify the roles of HIF1-AHNAK2 axis in inactivating the apoptosis pathway in hypoxia microenvirenment at cellular level, animal model level and clinical case analysis. This study will contribute to the exploration of potential novel targets for the treatment of NSCLC.