MKK4基因参与肿瘤发生发展，但其在肿瘤侵袭转移中的作用机制仍不明确。我们前期发现MKK4-1304T>G位点与肿瘤易感性相关，进而发现其与肠癌侵袭转移相关，生物信息学分析及功能实验揭示转录因子NKX2.1可能基于多态性位点调控MKK4，而MKK4表达改变影响上皮间质转化（EMT）相关标志物。因此，我们提出"NKX2.1基于MKK4-1304T>G位点多态性调控MKK4触发EMT途径促进或抑制肠癌的侵袭转移"的科学假设。并围绕该假设开展以下研究：探究MKK4-1304T>G位点多态性、MKK4、NKX2.1表达水平与肠癌侵袭转移的相关性；阐明NKX2.1基于MKK4-1304T>G位点多态性调控MKK4表达的分子机制；探讨NKX2.1/MKK4通过EMT途径促进或抑制肠癌侵袭转移机制。本研究将有助于揭示 NKX2.1/MKK4通路在肠癌侵袭转移中的分子机制，为指导肠癌靶向治疗提供科学依据。

The MKK4 gene involved in tumor development, but its role in tumor invasion and metastasis mechanism remains unclear. Our previous study found that MKK4-1304T> G single nucleotide polymorphism associated with cancer susceptibility, and then found that associated with colorectal cancer invasion and metastasis. Further, bioinformatics analysis and function experiments revealed that the transcription factor NKX2.1 may regulate the expression of MKK4 on the basis of MKK4 polymorphisms, while the expression of MKK4 changes affect epithelial mesenchymal transition (EMT) markers. Therefore, based on the previous research results, we proposed the scientific hypothesis that "NKX2.1 based on MKK4-1304T>G locus polymorphisms regulated the MKK4, and then activate EMT pathway to promote or inhibit the invasion and metastasis of colorectal cancer". In order to verify this hypothesis , The project intends to carry out the following research: first, to explore the correlation of MKK4-1304T> G polymorphism, MKK4, NKX2.1 expression levels and colorectal cancer invasion and metastasis; Second, to clarify the molecular mechanisms of NKX2.1 regulated the expression of MKK4 on based of MKK4-1304T> G polymorphisms state; Finally, to explore the mechanism that NKX2.1/MKK4 via EMT pathway to promote or inhibit colorectal cancer invasion and metastasis. This study will help to reveal the molecular mechanism of NKX2.1/MKK4 pathway in colorectal cancer invasion and metastasis, its completion will provide new candidate markers for CRC diagnosis and treatment, and new potential drug targets for treatment of CRC.