| RRC ID |
69810
|
| 著者 |
Hassan G, Zahra MH, Seno A, Seno M.
|
| タイトル |
The significance of ErbB2/3 in the conversion of induced pluripotent stem cells into cancer stem cells.
|
| ジャーナル |
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.
|
| 巻・号 |
12(1)
|
| ページ |
2711
|
| 公開日 |
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
|
| リソース情報 |
| ヒト・動物細胞 |
iPS-MEF-Ng-20D-17(APS0001)
PK-8(RCB2700) |
