CTHRC1 promotes growth, migration and invasion of trophoblasts via reciprocal Wnt/β-catenin regulation

Abstract

Preeclampsia (PE) is a pregnancy complication that is characterized by high blood pressure and is associated with high maternal and fetal morbidities. At a mechanistic level, PE is characterized by reduced invasion ability of trophoblasts. Collagen triple helix repeat containing-1 (CTHRC1) is a well-known tumor-promoting factor in several malignant tumors, but its role in trophoblasts remains unknown. In this study, we characterized the expression of CTHRC1 in placenta tissue samples from PE pregnancies and from normal pregnancies. We used the trophoblasts cell lines HTR-8/SVneo and JEG-3 to investigate the role of CTHRC1 in cell migration, invasion and proliferation. Western blot, PCR and TOP/FOP luciferase activity assays were used to investigate the molecular mechanisms underlying these cell behaviors. Placenta tissue samples obtained from pregnant women with PE expressed lower levels of CTHRC1 than those of placenta tissues from women with normal pregnancies. Down-regulation of CTHRC1 impaired cell proliferation, migration and invasion of trophoblasts, while CTHRC1 overexpression promoted nuclear translocation of β-catenin, a result that was further confirmed by TOP/FOP luciferase activity assay. Our findings suggest that CTHRC1 promotes migration and invasion of trophoblasts via reciprocal Wnt/β-catenin signaling pathway. Down-regulation of CTHRC1 may be a potential mechanism underpinning the development of preeclampsia.

Wnt signaling in colorectal cancer: pathogenic role and therapeutic target

“…The data shows that the oncogenic activation of KRAS/BRAF/MEK signals stimulates the classic Wnt/β-catenin pathway, which in turn promotes the growth and invasion of intestinal tumors [ 122 ]. CTHRC1 promotes growth, migration and invasion of trophoblasts via reciprocal Wnt/β-catenin regulation [ 123 ]. Initially, low expression of GAS5 was observed in colorectal cancer tissues and cells.…”

LncRNA HOXA11-AS promotes glioma malignant phenotypes and reduces its sensitivity to ROS via Tpl2-MEK1/2-ERK1/2 pathway

“…CTHRC1 activates β-catenin pathway by inducing its nuclear localization [ 24 , 25 ]. As HOXA11-AS increases CTHRC1 expression by serving as a ceRNA for let-7b-5p, we next investigated whether HOXA11-AS regulates the β-catenin pathway.…”

“…Studies have shown that c-Myc is an important transcription factor that regulates the transcription of multiple oncogenes [ 25 ]. The binding site of c-Myc was found in the HOXA11-AS promoter region in MCF-7 breast cancer cell lines from UCSC (Fig.…”

“…These results indicated that CTHRC1 is a direct target of HOXA11-AS/let-7b-5p. HOXA11-AS regulates the β-catenin/c-Myc pathway through let-7b-5p/CTHRC1 to form a unique self-activation loop CTHRC1 activates β-catenin pathway by inducing its nuclear localization [24,25]. As HOXA11-AS increases CTHRC1 expression by serving as a ceRNA for let-7b-5p, we next investigated whether HOXA11-AS regulates the β-catenin pathway.…”

“…We subsequently investigated whether CTHRC1 mediates HOXA11-AS activity in the β-catenin/c-Myc pathway. We performed c-Myc and Studies have shown that c-Myc is an important transcription factor that regulates the transcription of multiple oncogenes [25]. The binding site of c-Myc was found in the HOXA11-AS promoter region in MCF-7 breast cancer cell lines from UCSC (Fig.…”