CDCA8/SNAI2 Complex Activates CD44 to Promote Proliferation and Invasion of Pancreatic Ductal Adenocarcinoma

Abstract

(1) Background: Recently, cell division cycle associated 8 (CDCA8) was found to be overexpressed in pancreatic ductal adenocarcinoma (PDAC). Here, we aimed to explore the specific mechanism of action of CDCA8 in PDAC progression. (2) Methods: All human PDAC samples and clinical data were collected from Huashan Hospital, Fudan University. All experimental studies were carried out using many in vitro and in vivo assays, including lentiviral transfection, real-time quantitative polymerase chain reaction (qPCR), western blotting, co-immunoprecipitation (Co-IP), chromatin IP (ChIP)-qPCR, dual-luciferase reporter, and in vivo imaging assays. (3) Results: Clinical data analysis of human PDAC samples revealed that CDCA8 overexpression were positively and negatively associated with tumor grade (p = 0.007) and overall survival (p = 0.045), respectively. CDCA8 knockdown inhibited PDAC proliferation and invasion in in vitro and in vivo assays. CD44 was also up-regulated by CDCA8 during PDAC progression. CDCA8 could be combined with SNAI2 to form a CDCA8/SNAI2 complex to integrate with the CD44 promoter as indicated through ChIP-qPCR and dual-luciferase reporter assays. (4) Conclusion: We showed that CDCA8-CD44 axis plays a key role in the proliferation and invasion of PDAC, which provides a potential target for treatment.

Stemness subtypes in lower-grade glioma with prognostic biomarkers, tumor microenvironment, and treatment response

“…Of the four stemness model genes identified in this study, SMC4 regulates the cell cycle and impacts the proliferation, migration, and invasion of glioma 70 , 71 . CDCA8 is a cell cycle regulator and tumor promoter that produces a marked effect in various malignant tumors 72 . For example, it regulates the migration of glioma cells and inhibits cell apoptosis 73 .…”

CDCA gene family promotes progression and prognosis in lung adenocarcinoma

“…[21] CDCA8 also promotes the development of live cancer [22] and pancreatic cancer. [23] In this study, we intended to: Investigate the relationship between the expression of the CDCAs and clinical characteristics of patients with LUAD; analyze whether the CDCAs could serve as diagnostic and prognostic biomarkers in LUAD; evaluate the expression model of CDCAs to predict the survival time of individual patients; explore the known mechanisms using bioinformatics analysis.…”