FAM212B与DVLs结合促进非小细胞肺癌恶性表型的机制研究

FAM212B is a newly discovered protein whose expression and clinical pathological significance in human tumor is unclear. The molecular mechanism is still unknown. We found that FAM212B was highly expressed in NSCLC. The higher expression of FAM212B was correlated with malignant phenotype and poor prognosis. Up- or down-regulation of FAM212B could increase or decrease the proliferation, invasion and metastasis ability as well as the expression of relative proteins. We also demonstrated that FAM212B interacted with DVLs. Therefore, we propose that FAM212B may increase the expression of CyclinA2, CyclinB1 and Snail, decreased the expression of E-cadherin via JNK and/or AKT signaling pathway by binding with DVLs, and then enhanced the proliferation, invasion and metastasis of NSCLC. We will up- or down-regulated the expression of FAM212B and DVLs and construct different domain mutants of FAM212B and DVLs to clarify, both in vivo and in vitro, the interaction patterns of the FAM212B with DVLs and elucidate the mechanism on promoting proliferation, invasion and metastasis of NSCLC and further provided the experimental basis for the discovery of new markers of NSCLC and the development of targeted medicine.

FAM212B是一个新近被发现的蛋白，其在肿瘤组织中的表达、意义和作用机制尚不清楚。我们发现FAM212B在肺癌中高表达且与肺癌恶性表型和不良预后相关，双向调控其表达可增强或降低肺癌细胞增殖、侵袭转移能力和相关蛋白表达，FAM212B与DVLs存在相互作用。结合文献我们提出FAM212B与DVLs结合，通过JNK和/或AKT信号通路，上调CyclinA2, CyclinB1和Snail，下调E-cadherin的表达，促进肺癌细胞的增殖和侵袭能力。本研究拟采用双向调控FAM212B和DVLs，构建FAM212B与DVLs不能结合的突变质粒策略，并结合体外细胞功能试验和裸鼠移植试验证实，揭示FAM212B与DVLs的结合模式及促进肺癌增殖和侵袭的分子机制，为寻找新的非小细胞肺癌标记物和开发靶向治疗药物提供实验基础。

FAM212B是一个新近被发现的蛋白，其在肿瘤组织中的表达、意义和作用机制尚不清楚。 我们发现FAM212B在肺癌中高表达且与肺癌恶性表型和不良预后相关，双向调控其表达可增强或降低肺癌细胞增殖、侵袭转移能力和相关蛋白表达，FAM212B与DVLs存在相互作用。结合文献我们提出FAM212B与DVLs，Rac1结合，通过ERK信号通路，上调CyclinA2, CyclinB1和Snai l，下调E-cadherin的表达，促进肺癌细胞的增殖和侵袭能力。本研究发现FAM212B可能成为新的非小细胞肺癌标记物。