RRC ID 51951
Author Kumazoe M, Takai M, Bae J, Hiroi S, Huang Y, Takamatsu K, Won Y, Yamashita M, Hidaka S, Yamashita S, Yamada S, Murata M, Tsukamoto S, Tachibana H.
Title FOXO3 is essential for CD44 expression in pancreatic cancer cells.
Journal Oncogene
Abstract Pancreatic ductal adenocarcinoma (PDAC) is one of the most fatal types of cancer and the 5-year survival rate is only 5%. Several studies have suggested that cancer stem cells (CSCs) are thought to be involved in recurrence and metastasis and so it is essential to establish an approach targeting CSCs. Here we have demonstrated that cyclic guanosine monophosphate (cGMP) suppressed CD44 expression and the properties of CSCs in PDAC. Microarray analysis suggested that cGMP inhibited Forkhead box O3 (FOXO3), which is known as a tumor suppressor. Surprisingly, our data demonstrated that FOXO3 is essential for CD44 expression and the properties of CSCs. Our data also indicated that patients with high FOXO3 activation signatures had poor prognoses. This evidence suggested that cGMP induction and FOXO3 inhibition could be ideal candidates for pancreatic CSC.
Volume 36(19)
Pages 2643-2654
Published 2017-5-11
DOI 10.1038/onc.2016.426
PII onc2016426
PMID 27893718
MeSH Adenocarcinoma / genetics* Adenocarcinoma / pathology Animals Biomarkers, Tumor / biosynthesis Biomarkers, Tumor / genetics* Carcinoma, Pancreatic Ductal / genetics* Carcinoma, Pancreatic Ductal / pathology Cell Line, Tumor Cyclic GMP / metabolism Forkhead Box Protein O3 / biosynthesis Forkhead Box Protein O3 / genetics* Gene Expression Regulation, Neoplastic Humans Hyaluronan Receptors / biosynthesis Hyaluronan Receptors / genetics* Mice Microarray Analysis Neoplasm Metastasis Neoplastic Stem Cells / metabolism Neoplastic Stem Cells / pathology Prognosis Xenograft Model Antitumor Assays
IF 7.971
Times Cited 23
Human and Animal Cells PANC-1(RCB2095)