AKAP-9 promotes colorectal cancer development by regulating Cdc42 interacting protein 4

作者：Hu, Zhi-Yan; Liu, Yan-Ping; Xie, Lin-Ying; Wang, Xiao-Yan; Yang, Fang; Chen, Shi-You^*; Li, Zu-Guo^*

来源：Biochimica et Biophysica Acta-Molecular Basis of Disease, 2016, 1862(6): 1172-1181.

DOI：10.1016/j.bbadis.2016.03.012

• AKAP-9
• Colorectal cancer
• Metastasis
• Epithelial-mesenchymal transition
• Cdc42 interacting protein 4

Our previous studies have shown that PRKA kinase anchor protein 9 (AKAP-9) is involved in colorectal cancer (CRC) cell proliferation and migration in vitro. However, whether or not AKAP-9 is important for CRC development or metastasis in vivo remains unknown. In the present study, we found that AKAP-9 expression was significantly higher in human colorectal cancer tissues than the paired normal tissues. In fact, AKAP-9 level correlated with the CRC infiltrating depth and metastasis. Moreover, the higher AKAP-9 expression was associated with the lower survival rate in patients. In cultured CRC cells, knockdown of AKAP-9 inhibited cell proliferation, invasion, and migration. AKAP-9 deficiency also attenuated CRC tumor growth and metastasis in vivo. Mechanistically, AKAP-9 interacted with cdc42 interacting protein 4 (CIP4) and regulated its expression. CIP4 levels were interrelated to the AKAP-9 level in CRC cells. Functionally, AKAP-9 was essential for TGF-beta 1-induced epithelial-mesenchymal transition of CRC cells, and CIP4 played a critical role in mediating the function of AKAP-9. Importantly, CIP4 expression was significantly up-regulated in human CRC tissues. Taken together, our results demonstrated that AKAP-9 facilitates CRC development and metastasis via regulating CIP4-mediated epithelial-mesenchymal transition of CRC cells.

• 出版日期2016-6
• 单位南方医科大学