Abstract
Background/AimsGrowing evidence supports the direct link of Fusobacterium nucleatum with colorectal cancer (CRC). However, to date, the underlying mechanism of action remains poorly understood. In this study, we examined the effects of F. nucleatum on the progression of CRC and investigated whether cyclin-dependent kinase 5 (Cdk5) is involved in the effect through activating the Wnt/β-catenin signaling pathway.Materials and MethodsCRC tissues and matched histologically normal specimens were collected from patients who were diagnosed with CRC and underwent surgical treatment in our hospital between January 2018 and January 2019. Two human CRC cell lines, including DLD-1 and SW480, were utilized mainly for in vitro mechanistic investigations.ResultsThe abundance of F. nucleatum was significantly greater in CRC tissues than in cancer-free specimens, which was significantly correlated with the progression of CRC. In vitro investigations revealed that F. nucleatum significantly enhanced the proliferation and migration of CRC cells. Furthermore, F. nucleatum significantly induced the expression of Cdk5 and activation of the Wnt/β-catenin signaling pathway. Notably, knockdown of Cdk5 significantly abrogated the effects of F. nucleatum on cellular processes and Wnt/β-catenin signaling in relation to the progression of CRC.ConclusionThe results of this study demonstrate that F. nucleatum orchestrates a molecular network involving the direct role of Cdk5 in activating Wnt/β-catenin signaling to modulate CRC progression. Thus, in-depth investigations of F. nucleatum-associated molecular pathways may offer valuable insight into the pathogenesis of CRC, which may help further the development of treatment for this disease.
Highlights
Colorectal cancer (CRC) is among the most common malignancies in both males and females worldwide (Torre et al, 2015)
Zhang et al (2019) used quantitative PCR and bacterial 16S ribosomal RNA sequencing to show that the abundance of Fusobacterium nucleatum was significantly higher in both the tumor tissues and fecal specimens of CRC patients compared with healthy controls
We demonstrated that Cdk5 expression was significantly upregulated in CRC (Supplementary Figure S1), while knockdown of Cdk5 led to a significant reduction in the migration and invasive abilities of the DLD-1 and SW480 cells (Supplementary Figures S2–S4)
Summary
Colorectal cancer (CRC) is among the most common malignancies in both males and females worldwide (Torre et al, 2015). The number of intestinal microbes can be as high as 1014, which is approximately 10 times higher than the number of human cells in total. Advancements in DNA/RNA sequencing technology have allowed researchers to gain a better understanding of the composition and distribution of intestinal microbes. Zhang et al (2019) used quantitative PCR (qPCR) and bacterial 16S ribosomal RNA (rRNA) sequencing to show that the abundance of Fusobacterium nucleatum was significantly higher in both the tumor tissues and fecal specimens of CRC patients compared with healthy controls. Mima et al (2016) evaluated the predictive value of F. nucleatum for the prognosis of CRC in 1,069 CRC patients, suggesting that the higher abundance of F. nucleatum was significantly associated with shorter survival in patients with CRC.
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