JNK-Annexin A7 信号转导通路对小鼠腹水型肝癌干细胞生物学功能的影响

The lymphatic metastasis is one of main pattern in metastasis of hepatocellular carcinoma (HCC). The research of the molecular mechanism and signal transduction pathway could make great contribution to the clinic treatment by reducing the mortality of HCC. We have been found that the regulation of the expression of Annexin A7 was correlated with lymphatic metastasis in HCC. Annexin A7 may play an important role in lymphatic metastasis of HCC via JNK / P53 /Annexin VII and (/or) JNK / ATF-2 / CDH1 / Annexin VII signal transduction pathway (JNK-Annexin A7 pathway) which was identified by GeneGo software. In this research, CD133+ hepatic cancer stem cells (HCSCs) and CD133- cells will be screened from Hca-F cells and Hca-P cells, then the JNK gene in these cells will be down-regulated through either shRNA-lentivirus transfection technique or JNK signal transduction pathway blocking. The morphological changes, apoptosis, proliferation, migration in vitro and tumorigenesis in vivo will be observed in the cells which was down-reguleted via conversing JNK-Annexin A7 pathway. Our experiment will verify that Annexin A7 was correlated with lymphatic metastasis of HCC through the JNK-Annexin A7 signal transduction pathways. The results will provide theoretical and experimental basis for the decrease of lymphatic metastasis of HCC and early diagnosis and treatment of HCC in clinic.

淋巴道转移是肝癌转移的主要方式之一，其相关分子机制及信号转导通路的研究对降低肝癌死亡率有着重要的临床指导意义。本课题组前期研究证实，Annexin A7表达调控与小鼠腹水型肝癌淋巴道转移密切相关。通过GeneGo软件预测Annexin A7可能通过JNK/P53/Annexin VII 和（/或）JNK/ATF-2/CDH1/Annexin VII两条信号通路（JNK-Annexin A7通路）在肝癌淋巴道转移中起作用。本研究拟筛选Hca-F和Hca-P中CD133+肝癌干细胞和CD133-肝癌细胞，通过下调JNK基因和通路抑制剂调节上述信号通路后，观察体外细胞凋亡、增殖、迁移、形态变化及动物体内成瘤情况等生物学行为的变化，证实Annexin A7在小鼠腹水型肝癌淋巴道转移中可能通过上述信号通路起作用，为进一步发现有效降低肝癌淋巴道转移及临床肝癌转移早期诊治提供重要依据。