食管癌转移复发是影响患者长期生存的重要原因。前期工作表明，层粘连蛋白5γ2（Laminin 5γ2, LN-5γ2）在食管鳞癌组织中过表达，但其在食管癌转移复发中的作用及分子机理尚不清楚。免疫组化分析显示食管癌组织中LN-5γ2过表达与转移复发正相关。敲降LN-5γ2可明显抑制食管癌细胞的侵袭迁移。联合siRNA、western blot和回复实验证明MAP4是LN-5γ2的靶基因，并且LN-5γ2可正向调节MAP4的mRNA水平。据此我们提出假设，LN-5γ2通过调节转录因子活性进而激活MAP4相关信号通路，促进食管癌细胞侵袭迁移，导致食管癌转移复发。本课题旨应用分子生物学技术探究LN-5γ2调控MAP4的分子机制；利用动物模型和临床标本验证LN-5γ2/MAP4体内调控机制和临床意义。这将对于开发预警食管癌转移复发标志物，揭示内在机理，为今后食管癌临床治疗和改善预后提供理论依据。

Metastasis and recurrence are important factors for the long-term survival in esophageal squamous cell carcinoma (ESCC) patients. Our previous work showed that the expression of Laminin 5γ2 (LN-5γ2) was overexpressed in ESCC tissues. However, the role and molecular mechanism of LN-5γ2 in ESCC were not clear. Immunohistochemical analysis showed that over expression of LN-5γ2 was positively correlated with metastasis and recurrence of ESCC. LN-5γ2 inhibition significantly decreased cell invasion and migration compared to non-silenced and parental cells. Western blot and siRNA revealed that MAP4 was a downstream effector of LN-5γ2-induced invasion and migration. RT-PCR analysis suggested that mRNA levels of MAP4 was obviously inhibited in LN-5γ2-siRNA-transfected cells. Accordingly to these data, we propose the hypothesis that LN-5γ2 activates the MAP4 related signaling pathways by regulating the activity of transcription factors, and promotes cell invasion and migration, leading to metastasis and recurrence of ESCC. We will further apply techniques of molecular biology to explore the molecular mechanism between LN-5γ2 and MAP4; animal models and clinical samples to verify the internal regulation mechanism and clinical significance of LN-5γ2/MAP4. It will provide theoretical basis for developing the markers of metastasis and recurrence of ESCC, and reveal the molecular mechanisms of the invasion and migration of ESCC cells and tumor metastasis.