RRC ID 72965
Author Nakazato A, Mochizuki M, Shibuya-Takahashi R, Fujimori H, Fujii K, Saijoh S, Morita S, Yamazaki T, Imai T, Sato I, Satoh K, Yamaguchi K, Sugamura K, Yasuda J, Matsuura K, Shojaku H, Asada Y, Tamai K.
Title RELA is required for CD271 expression and stem-like characteristics in hypopharyngeal cancer.
Journal Sci Rep
Abstract CD271 (also referred to as nerve growth factor receptor or p75NTR) is expressed on cancer stem cells in hypopharyngeal cancer (HPC) and regulates cell proliferation. Because elevated expression of CD271 increases cancer malignancy and correlates with poor prognosis, CD271 could be a promising therapeutic target; however, little is known about the induction of CD271 expression and especially its promoter activity. In this study, we screened transcription factors and found that RELA (p65), a subunit of nuclear factor kappaB (NF-κB), is critical for CD271 transcription in cancer cells. Specifically, we found that RELA promoted CD271 transcription in squamous cell carcinoma cell lines but not in normal epithelium and neuroblastoma cell lines. Within the CD271 promoter sequence, region + 957 to + 1138 was important for RELA binding, and cells harboring deletions in proximity to the + 1045 region decreased CD271 expression and sphere-formation activity. Additionally, we found that clinical tissue samples showing elevated CD271 expression were enriched in RELA-binding sites and that HPC tissues showed elevated levels of both CD271 and phosphorylated RELA. These data suggested that RELA increases CD271 expression and that inhibition of RELA binding to the CD271 promoter could be an effective therapeutic target.
Volume 12(1)
Pages 17751
Published 2022-10-22
DOI 10.1038/s41598-022-22736-6
PII 10.1038/s41598-022-22736-6
PMID 36273237
PMC PMC9588052
MeSH Adapalene Cell Proliferation / genetics Humans Hypopharyngeal Neoplasms* / genetics Hypopharyngeal Neoplasms* / metabolism Hypopharyngeal Neoplasms* / pathology NF-kappa B / genetics NF-kappa B / metabolism Receptors, Nerve Growth Factor / genetics Receptors, Nerve Growth Factor / metabolism Transcription Factor RelA / genetics Transcription Factor RelA / metabolism
IF 3.998
Human and Animal Cells 293T(RCB2202)
DNA material Genome Network Project Human cDNA, IRAL050J02 (HGY100218)