J Cancer 2017; 8(13):2626-2635. doi:10.7150/jca.19381
CDC27 Induces Metastasis and Invasion in Colorectal Cancer via the Promotion of Epithelial-To-Mesenchymal Transition
1. Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou;
2. Department of Hematology/Oncology, Guangzhou Women and Children's Medical center, Guangzhou Medical University, Guangzhou, Guangdong;
3. Guangdong Lung Cancer Institute, Guangdong General Hospital and Guangdong Academy of Medical Sciences, Guangzhou.
* These authors contributed equally to this work
Qiu L, Tan X, Lin J, Liu Ry, Chen S, Geng R, Wu J, Huang W. CDC27 Induces Metastasis and Invasion in Colorectal Cancer via the Promotion of Epithelial-To-Mesenchymal Transition. J Cancer 2017; 8(13):2626-2635. doi:10.7150/jca.19381. Available from https://www.jcancer.org/v08p2626.htm
Distant metastasis is the primary cause of cancer-related death among patients with colorectal cancer (CRC), and the discovery of novel therapeutic targets by further exploring the molecular mechanisms of CRC metastasis is therefore urgently needed. We previously illustrated that CDC27 overexpression promoted proliferation in CRC, but no studies have emphasized the role of CDC27 in cancer metastasis thus far. Our previous data indicated that the expression of CDC27 was significantly associated with distant metastasis in patient tissues, and therefore, in this study, we focused on the investigation of the potential mechanisms of CDC27 in CRC metastasis. The results revealed that CDC27 promoted the metastasis, invasion and sphere-formation capacity of DLD1 cells, but that the inhibition of CDC27 in HCT116 cells suppressed metastasis both in vitro and in vivo. Mechanistic analyses revealed that CDC27 promoted epithelial-to-mesenchymal transition (EMT), as demonstrated by the reduced expression of the epithelial markers ZO-1 and E-cadherin and the enhanced expression of the mesenchymal markers ZEB1 and Snail in HCT116 and DLD1 cells. Further mechanistic investigation indicated that CDC27 promoted metastasis and sphere-formation capacity in an ID1-dependent manner. In conclusion, we first demonstrated the role of CDC27 in cancer metastasis and showed that CDC27 may serve as a promising therapeutic target for CRC.
Keywords: CDC27, colorectal cancer, metastasis, EMT, ID1