ANP32A参与MEK信号通路调控大肠癌细胞侵袭及迁移的功能及机制研究

Till now, the effective molecular targrt of metastasis haven't been found, so it is important to investigate the new target therapy markers of metastasis colorectal cancer. ANP32A is a multifunctional protein that regulates differentiation, transcription, apoptosis, and cell cycle progression. ANP32A has been considered a tumor suppressor, while recently it has been found involved in the invasion and migration of oral cancer, and can be a potential prognostic markers for oral cancer. We found that it is high expressed in colorectal cancer patients, and was positively correlated with tumor grading. But whether ANP32A is associated with colorectal cancer metastasis, and how its mechanism needs further study. Therefore, in this project, we will confirm its function from the following aspects: ① determine the position and expression of ANP32A in colorectal cancer cells; ② clarify the relationship between ANP32A and metastasis of colorectal cancer, reveal its mechanism; ③the correlation between ANP32A and EMT markers in colorectal cancer patients with its clinical significance. The completion of this project will help clarify the relationship between MEK signaling pathway and colorectal cancer metastasis; provide a new target for the early diagnosis and treatment of colorectal cancer.

目前晚期伴远处转移的大肠癌研究中尚未发现有效的分子靶向标记物，探索新的靶向治疗标记物及其分子机制对完善大肠癌转移机制的认识非常重要。ANP32A是一种具有多功能的蛋白质，具有调节分化，转录，调亡及细胞周期进程的功能。一直以来，它被认为是一种肿瘤抑制因子，但是最近发现其参与了口腔癌的转移，是口腔癌的潜在预后标记物。我们前期发现它在大肠癌患者的病理组织中高表达，与肿瘤的分级正相关。但是ANP32A是否与大肠癌转移相关，以及其机制如何需进一步研究。因此，在本项目中，我们将从以下几个方面进行确证：①确定ANP32A在大肠癌细胞中的定位与表达；② 明确ANP32A与大肠癌细胞迁移及侵袭能力的关系，阐明其作用机制；③大肠癌患者ANP32A及EMT标记物的表达及临床意义。本项目的完成将有助于阐明MEK信号通路与大肠癌转移的关系，为大肠癌的早期诊断和治疗提供新的靶点。