结直肠癌转移是困扰临床医生的一大难题，已经成为影响结直肠癌远期生存的主要因素之一。结直肠癌转移是一复杂的生物学过程，这一过程中，actin骨架重构介导的迁移侵袭起关键作用。本课题组在前期研究中发现，肿瘤抑制基因NDRG1能够通过介导ROCK1/pMLC2信号通路从而抑制actin骨架重构与应力纤维合成，进而抑制结直肠癌细胞迁移侵袭。有趣的是，在上述研究的同时，我们发现，阻断ROCK1/pMLC2信号通路后，这一现象未被完全逆转，提示可能存在NDRG1介导的其他信号通路参与NDRG1对actin骨架重构的调控。通过预实验的进一步验证，我们提出假说：NDRG1可能还通过与PKCδ的相互作用从而介导下游p21(CIP1/WAF1)/PAK1/MLCK/pMLC2信号通路进而介导结直肠癌细胞actin骨架重构。本课题旨在发现结直肠癌转移新机制，为转移性结直肠癌防治提供可能的新靶标及理论依据。

Metastasis, which is one of the key risk factors for long-term survival of colorectal cancer (CRC) patients, has gradually become one of the biggest clinical challenge. The metastasis of CRC is a complicated process, in which that cytoskeleton, especially actin cytoskeleton, plays the core effect in regulating cell migration and invasion. Our recent study has demonstrated that the novel tumor suppressor N-myc downstream regulated gene 1 (NDRG1) is able to resist CRC migration and invasion via inhibition of actin filament polymerization, stress fiber assembly, and cell migration as well as invasion through modulating the ROCK1/pMLC2 pathway. Interestingly, we also discovered that, if ROCK1/pMLC2 signaling was blocked, the resistance and inhibition effects of NDRG1 was only partially reversed. This indicates that there probably be other potential signaling pathways which may be involved in NDRG1-mediated actin cytockeleton remodeling. After a series of preliminary experiments, we raise the hypothesis as follows: NDRG1 may further regulate actin cytoskeleton remodeling through modulating p21(CIP1/WAF1)/PAK1/MLCK/pMLC2 signaling pathways; furthermore, this effect may on account of the protein-protein interaction between NDRG1 and the protein kinase C delta (PKCδ). This study may uncover the novel molecular mechanisms underlying the metastasis of CRC. Moreover, it may also provide theoretical evidences for the potential targeted therapy for metastatic CRC cases.