Abstract
DEP domain containing 1 (DEPDC1) is a newly identified cancer-related and cell cycle related gene and has been demonstrated as a novel therapeutic target for bladder cancer. However, the functional involvement and therapeutic potential of DEPDC1 in nasopharyngeal carcinoma (NPC) remains unclear. Our results showed that DEPDC1 was overexpressed at both mRNA and protein levels in NPC tissues compared with normal or non-tumor tissues. The siRNA-mediated DEPDC1 depletion resulted in significant inhibition of proliferation and delay in cell cycle progression in both NPC cell lines, CNE-1 and HNE-1. Detailed analysis with indirect immunofluorescence assays revealed that DEPDC1 depletion caused significant mitotic arrest accompanied with mitotic defects such as multipolar spindles and multiple nuclei followed by apoptotic cell death. Notably, DEPDC1 depletion also reduces migration and invasion ability in both cell lines. Consistent with its regulatory role in NF-κB pathway, knockdown of DEPDC1 caused significant upregulation of A20 and downregulation of mutiple NF-κB downstream target genes implicated in proliferation and tumorigenesis (c-Myc, BCL2, CCND1, CCNB1 and CCNB2), and metastasis (MMP2, MMP9, ICAM1, vimentin, Twist1). Moreover, in vivo study demonstrated that DEPDC1 knockdown also caused significant inhibition of tumor growth in the NPC xenograft nude mouse model. Taken together, our present study demonstrated that DEPDC1 is essentially required for the accelerated cell cycle progression and motility in NPC cells, and strongly suggested that DEPDC1 may serve as a novel therapeutic target in NPC.
Highlights
Nasopharyngeal carcinoma (NPC) is a type of head and neck cancer and shows unique geographical and ethnic distribution with high incidence in southeast Asia especially in the southern China [1,2,3]
Our present study demonstrated that DEP domain containing 1 (DEPDC1) is essentially required for the accelerated cell cycle progression and motility in nasopharyngeal carcinoma (NPC) cells, and strongly suggested that DEPDC1 may serve as a novel therapeutic target in NPC
Several studies have shown that DEPDC1 is aberrantly overexpressed in several types of cancers suggesting its therapeutic potential in cancers [8, 9, 12,13,14]
Summary
Nasopharyngeal carcinoma (NPC) is a type of head and neck cancer and shows unique geographical and ethnic distribution with high incidence in southeast Asia especially in the southern China [1,2,3]. Most commonly to lung, is the main cause of treatment failure, and the incidence of distant metastasis is higher in patients with advanced disease [4, 5]. Elucidation of the molecular mechanisms underlying the tumorigenesis, invasion and metastasis of NPC is critical for the treatment of this disease. DEP domain containing 1 (DEPDC1) is a recently identified novel tumor-related gene and highly conserved from Caenorhabditis elegans to human [8,9,10]. DEPDC1 is the human counterpart of LET-99 in Caenorhabditis elegans. The DEP (Dishevelled, EGL-10, Pleckstrin) domain exists in the N-terminal regions of both isoforms [9]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
