FOXD3 Suppresses Tumor-Initiating Features in Lung Cancer via Transcriptional Repression of WDR5
| Autor: | Xiaopan Cai, Wei Xu, Jianru Xiao, Xinghai Yang, Cong Jiang, Lei Li, Tianhui Hou, Haifeng Wei, Jialin Li, Tielong Liu |
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| Rok vydání: | 2019 |
| Předmět: |
Male
0301 basic medicine Lung Neoplasms animal structures Paclitaxel Cell Apoptosis Biology Metastasis Mice 03 medical and health sciences 0302 clinical medicine Cell Movement mental disorders medicine Animals Humans FOXD3 Lung cancer Cell Proliferation Intracellular Signaling Peptides and Proteins Forkhead Transcription Factors Cell migration Cell Biology medicine.disease Embryonic stem cell Gene Expression Regulation Neoplastic 030104 developmental biology medicine.anatomical_structure A549 Cells Doxorubicin Drug Resistance Neoplasm Tumor progression embryonic structures Neoplastic Stem Cells Cancer research Heterografts Molecular Medicine Female Stem cell 030217 neurology & neurosurgery Developmental Biology |
| Zdroj: | Stem Cells. 37:582-592 |
| ISSN: | 1549-4918 1066-5099 |
| DOI: | 10.1002/stem.2984 |
| Popis: | The tumor-initiating cells (TICs) are a cell population that can initiate tumor occurrence, mediate drug resistance, and give rise to metastasis. FOXD3 is a forkhead box (Fox) transcription factor family that regulates the pluripotency of embryonic stem cell and tumorigenicity. However, it is unclear whether FOXD3 plays any role in TIC and tumor metastasis. The functional analysis of FOXD3 was performed by oncospheres formation and redifferentiation, drug resistance assay, and cell migration. Global genomic RNA-Seq and ChIP-Seq analysis were used to identify the direct target of FOXD3 in lung cancer. We demonstrated that downregulation of FOXD3 in TICs was positively correlated with higher histologic grades and positive lymph node metastasis. FOXD3 repressed TIC expansion and cell migration, drug resistance, and osteoclasts in vitro and in vivo. Mechanically, we found that FOXD3 represses WDR5, which regulates TIC-related signaling pathway. Moreover, WDR5 were positively correlated with the TIC abundance and tumor progression. Besides, patients with high expression of WDR5 presented a poorer overall survival. FOXD3 may suppress TIC accumulation by repressing the expression of WDR5 in lung cancer. Stem Cells 2019;37:582–592 |
| Databáze: | OpenAIRE |
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