Schistosoma mansoni eggs induce Wnt/β-catenin signaling and activate the protooncogene c-Jun in human and hamster colon

Abstract

Schistosomiasis (bilharzia) is a neglected tropical disease caused by parasitic flatworms of the genus Schistosoma, with considerable morbidity in parts of the Middle East, South America, Southeast Asia, in sub-Saharan Africa, and particularly also in Europe. The WHO describes an increasing global health burden with more than 290 million people threatened by the disease and a potential to spread into regions with temperate climates like Corsica, France. The aim of our study was to investigate the influence of S. mansoni infection on colorectal carcinogenic signaling pathways in vivo and in vitro. S. mansoni infection, soluble egg antigens (SEA) and the Interleukin-4-inducing principle from S. mansoni eggs induce Wnt/β-catenin signaling and the protooncogene c-Jun as well as downstream factor Cyclin D1 and markers for DNA-damage, such as Parp1 and γH2a.x in enterocytes. The presence of these characteristic hallmarks of colorectal carcinogenesis was confirmed in colon biopsies from S. mansoni-infected patients demonstrating the clinical relevance of our findings. For the first time it was shown that S. mansoni SEA may be involved in the induction of colorectal carcinoma-associated signaling pathways.

Does Schistosoma Mansoni Facilitate Carcinogenesis?

“…Previously, we reported the upregulation of the JNK/c-Jun signaling pathway in the liver of S. mansoni-infected hamsters, human liver samples, and primary liver cells exposed to S. mansoni SEA [106]. Interestingly, a similar activation pattern of the proto-oncogene c-Jun was discovered in epithelial colon cells and colon specimens exposed to S. mansoni SEA [105]. Urothelial cells co-cultured with either S. mansoni eggs or S. haematobium eggs resulted in the upregulation of WNT5a and WNT5b, which have been implicated in CRC via the non-canonical WNT signaling pathway [161].…”

“…Urothelial cells co-cultured with either S. mansoni eggs or S. haematobium eggs resulted in the upregulation of WNT5a and WNT5b, which have been implicated in CRC via the non-canonical WNT signaling pathway [161]. Activation of the non-canonical WNT signaling pathway was also found in epithelial colon cells exposed to SEA [105]. Hence, it can be speculated that the carcinogenicity of chronic infection with schistosomes may not only depend on the schistosome species but also on the host tissue exposed to SEA.…”

“…Metabolic changes correlated with the eggs deposited in the liver have been shown in S. japonicuminfected mice, indicating the promotion of glycolysis-related genes on the one hand and downregulation of gluconeogenesis-related genes on the other hand [104]. In addition to the metabolic changes induced by the schistosome ova, SEA have the potential to alter cancerogenic signaling at the molecular level in vitro and in vivo [105,106]. In cancer progression, metabolic reprogramming, oxidative stress, and DNA damage display crucial events.…”

Cyclic Mechanical Strain Regulates Osteoblastic Differentiation of Mesenchymal Stem Cells on TiO2 Nanotubes Through GCN5 and Wnt/β-Catenin

“…GSK3β can phosphorylate β-catenin and then β-catenin could be hydrolyzed by APC complex. Its downregulation makes β-catenin accumulate in the cytoplasm, which then migrates into the nucleus and when combined with TCF/LEF transcription factors affects the transcription of target genes ( Weglage et al, 2020 ). The Wnt/β-catenin signaling pathway is an important pathway in the process of cell differentiation.…”

Hepatic Topology of Glycosphingolipids in Schistosoma mansoni-Infected Hamsters

“…mansoni cercariae (bs-infected), hamsters infected with only one sex of S. mansoni cercariae (ss-infected), and noninfected hamsters. − For each group, three randomly chosen biological replicates were used throughout the study.…”