Abstract
Coiled-coil domain-containing 68 (CCDC68) plays different roles in cancer and is predicted as a tumor suppressor in human colorectal cancer (CRC). However, the specific role of CCDC68 in CRC and the underlying mechanisms remain unknown. Here, we showed that CCDC68 expression was lower in CRC than that in corresponding normal tissues, and CCDC68 level was positively correlated with disease-free survival. Ectopic expression of CCDC68 decreased CRC cell proliferation in vitro and suppressed the growth of CRC xenograft tumors in vivo. CCDC68 caused G0/G1 cell cycle arrest, downregulated CDK4, and upregulated ITCH, the E3 ubiquitin ligase responsible for CDK4 protein degradation. This increased CDK4 degradation, which decreased CDK4 protein levels and inhibited CRC tumor growth. Collectively, the present results identify a novel CDK4 regulatory axis consisting of CCDC68 and ITCH, which suggest that CCDC68 is a promising target for the treatment of CRC.
Highlights
Colorectal cancer (CRC), one of the three most common cancers worldwide, has the third highest incidence rate (10%) and the second highest mortality rate (9.4%), and is a considerable threat to human life and health [1]
The results showed that Coiled-coil domain-containing 68 (CCDC68) was significantly downregulated in tumor tissues, which was consistent with the Cancer Genome Atlas (TCGA) data (Figures 1B–D)
CCDC68 is upregulated in non-small cell lung cancer (NSCLC), and downregulating CCDC68 expression decreases cell proliferation and increases apoptosis, suggesting that CCDC68 is a candidate biomarker for the detection of malignant transformation in lung cancer [16]
Summary
Colorectal cancer (CRC), one of the three most common cancers worldwide, has the third highest incidence rate (10%) and the second highest mortality rate (9.4%), and is a considerable threat to human life and health [1]. The occurrence and development of CRC are mediated by a complex process that involves multiple pathways [2, 3], such as the EGFR, Wnt/b-catenin, TGF-b, and Sonic Hedgehog pathways. The factors and/or genes involved in these pathways may be potential therapeutic targets in CRC [4, 5]. The combination of panitumumab, a human monoclonal antibody against EGFR, with supportive therapy is a common strategy for the treatment of metastatic CRC [6]. Several inhibitors of the Wnt/b-catenin signaling pathway have been developed for the treatment of CCDC68 Inhibits CRC Cell Growth
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