DEPDC1 is required for cell cycle progression and motility in nasopharyngeal carcinoma

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.

Oncogenic hijacking of a developmental transcription factor evokes therapeutic vulnerability for ROS-induction in Ewing sarcoma

“…Among the proliferation-associated genes downregulated after SOX6 knockdown ( Fig. 3b), three genes (CDCA3, DEPDC1 and E2F8) appeared as plausible candidate genes to promote the pro-proliferative phenotype of SOX6, as they were previously shown to be involved in cell cycle progression [29][30][31][32] . In accordance, knockdown of any one of the genes with specific sipools in RDES and TC-32 EwS cells phenocopied, at least in part, the proliferative effect of SOX6 ( Supplementary Fig.…”

DEPDC1 drives hepatocellular carcinoma cell proliferation, invasion and angiogenesis by regulating the CCL20/CCR6 signaling pathway

“…Previous studies have indicated that DEPDC1 is elevated in several types of cancer and is implicated in tumorigenesis (6)(7)(8)(9)(10). It has also been revealed that DEPDC1 is upregulated in HCC tissue and may therefore be an independent predictor of HCC (11).…”

“…It is primarily expressed in the testis and is not detected in other normal human tissues (6). Recently, several studies revealed that DEPDC1 was upregulated in many tumor types, indicating its important role in tumorigenesis (7)(8)(9)(10). For example, DEPDC1 was upregulated in bladder carcinogenesis and the inhibition of DEPDC1 via small-interfering RNA (siRNA) significantly suppressed the growth of bladder cancer cells (7).…”

“…For example, DEPDC1 was upregulated in bladder carcinogenesis and the inhibition of DEPDC1 via small-interfering RNA (siRNA) significantly suppressed the growth of bladder cancer cells (7). In nasopharyngeal carcinoma, DEPDC1 was overexpressed in tumor tissues and DEPDC1 depletion induced the inhibition of cell proliferation, migration and invasion (9). Thus, DEPDC1 usually functions as an oncogene.…”

DEP domain containing 1 predicts prognosis of hepatocellular carcinoma patients and regulates tumor proliferation and metastasis

“…Several studies have shown that DEPDC1 is aberrantly overexpressed in diverse human cancers and acts as an oncogene in tumorigenesis and tumor progression. [23][24][25][26] In a previous study, Feng et al 27 reported that DEPDC1 is essentially required for accelerating cell cycle progression and motility in nasopharyngeal carcinoma through the NF-κB signal pathway. In another study, researchers discovered an oncogenic role of DEPDC1 in prostate cancer through activation of E2F signaling which has a broad impact on HCC progression.…”