RRC ID 69810
Author Hassan G, Zahra MH, Seno A, Seno M.
Title The significance of ErbB2/3 in the conversion of induced pluripotent stem cells into cancer stem cells.
Journal Sci Rep
Abstract Cancer stem cells (CSCs) are suggested to be responsible for drug resistance and aggressive phenotypes of tumors. Mechanisms of CSC induction are still under investigation. Our lab has established a novel method to generate CSCs from iPSCs under a cancerous microenvironment mimicked by the conditioned medium (CM) of cancer-derived cells. Here, we analyzed the transcriptome of CSCs, which were converted from iPSCs with CM from pancreatic ductal adenocarcinoma cells. The differentially expressed genes were identified and used to explore pathway enrichment. From the comparison of the CSCs with iPSCs, genes with elevated expression were related to the ErbB2/3 signaling pathway. Inhibition of either ErbB2 with lapatinib as a tyrosine kinase inhibitor or ErbB3 with TX1-85-1 or siRNAs arrested cell proliferation, inhibited the in vitro tumorigenicity, and lead to loss of stemness in the converting cells. The self-renewal and tube formation abilities of cells were also abolished while CD24 and Oct3/4 levels were reduced, and the MAPK pathway was overactivated. This study shows a potential involvement of the ErbB2/ErbB3 pathway in CSC generation and could lead to new insight into the mechanism of tumorigenesis and the way of cancer prevention.
Volume 12(1)
Pages 2711
Published 2022-2-17
DOI 10.1038/s41598-022-04980-y
PII 10.1038/s41598-022-04980-y
PMID 35177646
PMC PMC8854581
MeSH Acrylamides / pharmacology Adenine / analogs & derivatives Adenine / pharmacology Carcinoma, Pancreatic Ductal / metabolism Cell Line, Tumor Cell Proliferation / drug effects Cell Proliferation / genetics Cell Self Renewal / drug effects Culture Media, Conditioned Gene Expression Regulation, Neoplastic Humans Induced Pluripotent Stem Cells / metabolism* Lapatinib / pharmacology MAP Kinase Signaling System Neoplastic Stem Cells / metabolism* Pancreatic Neoplasms / metabolism Protein Kinase Inhibitors / pharmacology Receptor, ErbB-2 / antagonists & inhibitors Receptor, ErbB-2 / metabolism* Receptor, ErbB-3 / antagonists & inhibitors Receptor, ErbB-3 / genetics Receptor, ErbB-3 / metabolism* Signal Transduction
IF 3.998
Human and Animal Cells iPS-MEF-Ng-20D-17(APS0001) PK-8(RCB2700)