PYGO in Cancer Pathway
Division of Risk Assessment, Center for Biological Safety and Research, National Institute of Health Sciences, Kawasaki 210-9501, Japan
*Corresponding author: Shihori Tanabe, Division of Risk Assessment, Center for Biological Safety and Research, National Institute of Health Sciences, Kawasaki 210-9501, Japan
Citation: Tanabe S. (2023) PYGO in Cancer Pathway. Adv Clin Med Res. 4(1):1-3.
Received: January 20, 2023 | Published: February 06, 2023
Copyright© 2023 by Tanabe S. All rights reserved. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Several molecules are involved in cancer molecular network. Pygopus family plant homeodomain (PHD) finger (Pygo) is a component of Wnt/b-catenin transcription complex. Pygo has two homologs, Pygo1 and Pygo2, in mammalian cells. Pygo2 has an important role as a component of b-catenin - B-cell CLL/lymphoma 9 (Bcl9)-TCF/LEF complex. In this Editorial, a role of Pygo in Wnt/b-catenin signaling related to cancer pathway is summarized.
What is PYGO?
Pygopus family plant homology domain (PHD) finger (Pygo) is a dedicated component of the Wnt/b-catenin transcription complex . Pygo is required for MYC, a basic helix-loop-helix leucine zipper protein, -dependent activation of mitosis-related genes and an essential component of MYC oncogenic activity . Pygo has two homologs in mammalian cells, which are Pygo1, dispensable for normal murine development, and Pygo2, related to malignant growth in different cancers . Pygo2 binds specific histone marks of activation such as H3K4me3, which promotes an open euchromatic structure as transcribing genes . Pygo2 participates in the expression of highly transcribed RNAs essential for DNA replication and cell-cycle progression .
PYGO in Wnt/b-catenin signaling
Pygo is necessary for virtually all canonical Wnt signaling-dependent responses . It has been demonstrated that mutations in B-cell CLL/lymphoma 9 (Bcl9) and Pygo genes result in congenital heart defects by tissue-specific perturbation of Wnt/b-catenin signaling in zebrafish . The interaction between Pygo2 and di- and trimethylated lysine 4 of histone H3 (H3K4me2/3) is essential for mouse development and Wnt signaling-dependent transcription . Pygo2 is more popular than Pygo1 in development, while Pygo1 and Pygo2 are considered to be tissue-specific Wnt pathway components . Pygo2 is recruited by Bcl9 and Bcl9-like (Bcl9l) (Bcl9/9l) and sustains Pax6 expression to ensure a correct lens development in mice, independent of b-catenin .
PYGO in therapeutic-resistant cancer
It has been reported that the interactions of Bcl9/Bcl9L with b-catenin and Pygo promote breast cancer growth, invasion, and metastasis . Bcl9/Bcl9L bind to Pygo and to the N-terminal domain of b-catenin via the homology domain 1 (HD1) and HD2 domains [5,6]. PYGO2 gene expression was down-regulated in diffuse-type gastric cancer compared to intestinal-type gastric cancer . Diffuse-type gastric cancer demonstrates epithelial-mesenchymal transition-like phenotype which is related to therapeutic resistance in cancer . Some correlations between PYGO2 expression and therapeutic-resistant cancer have been reported. Pygo promotes transcriptional activation of Wnt-target genes via b-catenin . It may be possible that PYGO2 in Bcl9-TCF complex contributes to cancer progression in terms of Wnt/b-catenin pathway.
Pygo2 play a role in cancer pathway especially in correlation of Wnt/b-catenin pathway. PYGO2 expression seems to be associated with cancer phenotypes, whereas precise mechanism of the Pygo2-promoted therapeutic resistance in cancer is a way of the future.
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