title: AKAP-9 promotes colorectal cancer development by regulating Cdc42 interacting protein 4.
abstract: 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-β1-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.
authors.affiliation: Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China; Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China; Guangdong Provincial Key Laboratory of Molecular Tumour Pathology, Guangzhou 510515, China.
authors.forename: Zhi-Yan
authors.initials: ZY
authors.lastname: Hu
authors.affiliation: Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China; Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China; Guangdong Provincial Key Laboratory of Molecular Tumour Pathology, Guangzhou 510515, China.
authors.forename: Yan-Ping
authors.initials: YP
authors.lastname: Liu
authors.affiliation: Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China; Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China; Guangdong Provincial Key Laboratory of Molecular Tumour Pathology, Guangzhou 510515, China.
authors.forename: Lin-Ying
authors.initials: LY
authors.lastname: Xie
authors.affiliation: Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China; Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China; Guangdong Provincial Key Laboratory of Molecular Tumour Pathology, Guangzhou 510515, China.
authors.forename: Xiao-Yan
authors.initials: XY
authors.lastname: Wang
authors.affiliation: Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China; Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China; Guangdong Provincial Key Laboratory of Molecular Tumour Pathology, Guangzhou 510515, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Yang
authors.affiliation: Department of Physiology & Pharmacology, University of Georgia, Athens, GA, United States. Electronic address: sc229@uga.edu.
authors.forename: Shi-You
authors.initials: SY
authors.lastname: Chen
authors.affiliation: Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China; Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China; Guangdong Provincial Key Laboratory of Molecular Tumour Pathology, Guangzhou 510515, China. Electronic address: Lizg@smu.edu.cn.
authors.forename: Zu-Guo
authors.initials: ZG
authors.lastname: Li
mesh_terms: D054758:A Kinase Anchor Proteins / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000378:metabolism / Q000473:pathology*; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism*; D058750:Epithelial-Mesenchymal Transition; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D015778:Minor Histocompatibility Antigens / Q000235:genetics / Q000378:metabolism*; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000473:pathology*; D060066:Protein Interaction Maps
chemical_list: D054758:A Kinase Anchor Proteins; C119719:AKAP9 protein, human; D003598:Cytoskeletal Proteins; D008869:Microtubule-Associated Proteins; D015778:Minor Histocompatibility Antigens; C406285:TRIP10 protein, human
keywords: AKAP-9; Cdc42 interacting protein 4; Colorectal cancer; Epithelial-mesenchymal transition; Metastasis