近年来，结直肠癌的发病率在中国呈现逐年上升的趋势，其发病机制尚未完全明确。我们前期研究发现NLK在结直肠癌症细胞核中表达量异常增高，促进结直肠癌细胞的生长和增殖，但在肿瘤晚期NLK过表达能抑制肿瘤转移，因此NLK在结直肠癌中的作用及其机制仍不清晰。初步实验证明NLK一方面通过HDAC1/E2F1转录复合物促进肿瘤生长；另一方面通过抑制Nedd9表达，从而抑制肿瘤转移，但具体机制有待进一步证明。为此基于此，我们提出假说，NLK在结直肠癌发生早期，磷酸化HDAC1削弱HDAC1对E2F1的去乙酰化作用，促进细胞周期从而促进肿瘤生长；在晚期，NLK抑制Nedd9的表达，削弱了TGFβ信号通路，抑制肿瘤转移。该假说的证明将阐明NLK在结直肠癌发生发展和转移中的功能，为进一步揭示结直肠癌的发病机制，为早期诊断、靶向治疗及预后判断提供重要的理论依据。

Colorectal cancer (CRC) is one of the most common malignancies. Our study showed the high expression of NLK in colorectal cancer promoted colorectal cancer cell growth and proliferation in the early stage, but inhibits tumor metastasis in the late stage. The functions of NLK in colorectal cancer are unclear. Preliminary experiments showed that NLK promoted tumor growth through regulating transcription of HDAC1/E2F1 complex. On the other hand, NLK inhibited expression of Nedd9 to inhibit tumor metastasis, but the mechanism needs to be further proved. So we propose that in the early stage of colorectal cancer, the deacetylation of E2F1 by HDAC1 is weaken due to phosphorylation of HDAC1 by NLK, and then promotes tumor growth. In the late stage, NLK inhibits the expression of Nedd9 and inhibits tumor metastasis. The study provides important theoretical basis for early diagnosis, treatment and prognosis judgement.