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XPNPEP3 is a novel transcriptional target of canonical Wnt/β‐catenin signaling
Author(s) -
Kumar Raju,
Kotapalli Viswakalyan,
Naz Ashmala,
Gowrishankar Swarnalata,
Rao Satish,
Pollack Jonathan R,
Bashyam Murali Dharan
Publication year - 2018
Publication title -
genes, chromosomes and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.754
H-Index - 119
eISSN - 1098-2264
pISSN - 1045-2257
DOI - 10.1002/gcc.22531
Subject(s) - wnt signaling pathway , axin2 , biology , cancer research , tissue microarray , colorectal cancer , ectopic expression , transcriptome , catenin , microarray analysis techniques , beta catenin , microarray , lrp6 , downregulation and upregulation , signal transduction , cancer , microbiology and biotechnology , gene expression , cell culture , gene , genetics
Canonical Wnt/β‐catenin signaling plays important roles in embryonic development and adult tissue regeneration while aberrant Wnt activation is the major driver of sporadic colorectal cancer (CRC). Thus, it is important to characterize the complete β‐catenin target transcriptome. We previously performed microarray‐based mRNA profiling of rectal cancer samples stratified for Wnt status. In addition to AXIN2 and EPHB2 , XPNPEP3 transcripts were significantly elevated in tumors exhibiting activated Wnt/β‐catenin signaling, validated by Q‐PCR. Three different cell lines supported elevated XPNPEP3 transcript levels upon activation of Wnt signaling, confirmed using promoter‐luciferase assays. Ectopic expression of XPNPEP3 promoted tumorigenic properties in CRC cells. Immunohistochemistry on a CRC tissue microarray revealed significant correlation between β‐catenin nuclear localization and XPNPEP3 levels. More importantly, XPNPEP3 expression was upregulated compared to normal samples in published expression data sets from several cancers including CRC. Finally, XPNPEP3 expression correlated with poor survival in many cancers. Our results therefore suggest XPNPEP3 to be a transcriptional target of Wnt/β‐catenin pathway with particular significance for CRC.