Wnt/β-Catenin Pathway Is Regulated by PITX2 Homeodomain Protein and Thus Contributes to the Proliferation of Human Ovarian Adenocarcinoma Cell, SKOV-3

Abstract

Background: Wnt pathway and homeodomain proteins are associated with cancer, but their interaction in ovarian cancer cells has not been studied. Results: PITX2 itself and through inducing Wnt ligands activates the canonical Wnt pathway and cell proliferation. Downregulation of Frizzled receptors limits further Wnt activation. Conclusion: PITX2 enhances proliferation of SKOV-3 cells by inducing canonical Wnt signaling. Significance: This study will help understand the mechanism of proliferation in ovarian cancer cells.

Downregulation of MicroRNA-644a Promotes Esophageal Squamous Cell Carcinoma Aggressiveness and Stem Cell–like Phenotype via Dysregulation of PITX2

“…Various studies have documented that the Wnt/b-catenin signaling pathway is constitutively activated in many types of human cancer, and plays an important role in triggering aggressive cellular features that constitute a malignant phenotype (23)(24)(25). It was reported that PITX2 and the Wnt/b-catenin pathway exert positive-feedback regulation, while aberrant activation of Wnt/b-catenin signaling is strongly involved in ESCC tumorigenesis and/or progression (8,26). These results collectively suggest that the Wnt/b-catenin axis is one of the critical downstream pathways activated by PITX2 accumulation in ESCC malignancy that we now propose is miR-644a-mediated.…”

“…As previous study suggested that PITX2 crosstalks with the Wnt/b-catenin pathway (7,8), we sought to use miR-644a to probe the role of PITX2 in Wnt/b-catenin signaling. We demonstrated that miR-644a overexpression in ESCC cells reduced the pool of activated b-catenin (i.e., dephosphorylated at Ser37 and Ser41), nuclear b-catenin, and the typical downstream target genes of b-catenin (Fig.…”

“…Pairedlike homeodomain transcription factor 2 (PITX2) is a member of the bicoid-related homeodomain family and a downstream effecter of Wnt signaling, which activates the expression of target genes required for cell proliferation and survival (7). In addition to its regulation by Wnt, PITX2 itself could directly activate Wnt ligand genes, activating the respective canonical Wnt/b-catenin signaling pathway, thus contributing to cancer progression (8). Overexpression of PITX2 has been frequently studied in human cancers, including thyroid, colorectal, and ovarian cancers (9)(10)(11).…”

The novel 22 bp insertion mutation in a promoter region of the <i>PITX2</i> gene is associated with litter size and growth traits in goats

“…The significant effects of the 22 bp indel on reproductive traits might be explained by the function of the PITX2 gene: first, as a member of POU1F1-PROP1 pathway, the PITX2 gene regulates transcription and expression of other genes such as POU1F1, LHX3, PROP1, GH, and PRL (Zhang et al, 2015;Bertko et al, 2017;Zhao et al, 2017). Second, the PITX2 gene regulates Wnt/β-catenin pathway, affecting embryo implantation (Yusuke et al, 2006;Basu et al, 2013;Yeonsoo et al, 2015); therefore, this might be linked to litter size. Third, the PITX2 gene also regulates multiplets by influencing embryo polarity and axis formation (Angela et al, 2014).…”

“…(1) In Wnt/β-catenin signal pathway, the PITX2 gene not only activates the canonical pathway by itself and by inducing Wnt ligands but also limits further Wnt activation by down-regulating frizzled receptors. The PITX2 gene can also mediate mRNA stabilization in the Wnt/β-catenin pathway (Basu et al, 2013). Essential role played by Wnt/β-catenin signal pathway in regulation of progenitor cell fate, development decisions, proliferation during embryonic development, and adult tissue homeostasis is known (Maryam et al, 2018).…”