Open AccessTranscription factor POU4F2 promotes colorectal cancer cell migration and invasion through hedgehog‐mediated epithelial‐mesenchymal transition
Author(s) -
Guo Kaibo,
Wang Peipei,
Zhang Leyin,
Zhou Yiwen,
Dai Xinyang,
Yan Yici,
Chen Yuxuan,
Wasan Harpreet S.,
Yu Jieru,
Ruan Shanming,
Sun Leitao
Publication year - 2021
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.15089
Subject(s) - smoothened , cancer research , epithelial–mesenchymal transition , hedgehog , hedgehog signaling pathway , biology , transcription factor , cell migration , gli1 , gene knockdown , downregulation and upregulation , metastasis , gene silencing , signal transduction , microbiology and biotechnology , cell , cancer , cell culture , genetics , gene
Abstract As a POU homeodomain transcription factor, POU4F2 has been implicated in regulating tumorigenic processes in various cancers. However, the role of POU4F2 in colorectal cancer (CRC) remains unclear. Here, we revealed that POU4F2 functions as a tumor promotor in CRC. Bioinformatics analysis in specimens from CRC patients and expression analysis in CRC cell lines showed that POU4F2 was upregulated at the mRNA and protein levels in CRC. Depletion of POU4F2 suppressed the metastatic phenotypes of CRC cells, including cell migration, invasion, and the expression of epithelial‐mesenchymal transition (EMT) markers. Moreover, depletion of POU4F2 decreased the number of lung metastatic nodes in nude mice. Mechanistically, POU4F2 positively regulated the Hedgehog signaling pathway, as inferred from the downregulation of the expression of sonic Hedgehog homolog, patched 1, Smoothened, and GLI family zinc finger 1 in vitro and vivo following silencing of POU4F2. Furthermore, the SMO agonist SAG reversed the effects of POU4F2 knockdown in CRC. Functionally, POU4F2 contributed to the Hedgehog signaling‐regulated activation of the EMT process and promotion of CRC cell migration and invasion. Collectively, these findings elucidated the role of POU4F2 as a tumor promotor in CRC through the regulation of Hedgehog signaling‐mediated EMT and suggested that POU4F2 suppression might be a promising therapeutic target in inhibiting CRC metastasis.