FOXF1 mediates mesenchymal stem cell fusion-induced reprogramming of lung cancer cells
Autor: | Jac A. Nickoloff, Wen Cheng Lo, David F. Williams, Wei Hong Chen, Ya Ting Chang, Cheng-Wen Wu, Hong-Jian Wei, Pan-Chyr Yang, Juri G. Gelovani, Win Ping Deng, Hen Yu Liu |
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Jazyk: | angličtina |
Rok vydání: | 2014 |
Předmět: |
Cyclin-Dependent Kinase Inhibitor p21
Stromal cell Lung Neoplasms Mice SCID Biology Mice Spheroids Cellular medicine Tumor Cells Cultured Tumor Microenvironment Animals Humans RNA Small Interfering FOXF1 lung cancer cell mesenchymal stem cell Cell Proliferation Tumor microenvironment Cell fusion cell fusion p21 Cell growth Mesenchymal stem cell Cancer reprogramming Forkhead Transcription Factors Mesenchymal Stem Cells medicine.disease Cellular Reprogramming Cell biology Oncology Cell Transdifferentiation Cancer research Female RNA Interference Reprogramming Research Paper |
Zdroj: | Oncotarget |
ISSN: | 1949-2553 |
Popis: | Several reports suggest that malignant cells generate phenotypic diversity through fusion with various types of stromal cells within the tumor microenvironment. Mesenchymal stem cell (MSC) is one of the critical components in the tumor microenvironment and a promising fusogenic candidate, but the underlying functions of MSC fusion with malignant cell have not been fully examined. Here, we demonstrate that MSCs fuse spontaneously with lung cancer cells, and the latter is reprogrammed to slow growth and stem-like state. Transcriptome profiles reveal that lung cancer cells are reprogrammed to a more benign state upon MSC fusion. We further identified FOXF1 as a reprogramming mediator that contributes not only to the reprogramming toward stemness but also to the p21-regulated growth suppression in fusion progeny. Collectively, MSC fusion does not enhance the intrinsic malignancy of lung cancer cells. The anti-malignant effects of MSC fusion-induced reprogramming on lung cancer cells were accomplished by complementation of tumorigenic defects, including restoration of p21 function and normal terminal differentiation pathways as well as up-regulation of FOXF1, a putative tumor suppressor. Such fusion process raises the therapeutic potential that MSC fusion can be utilized to reverse cellular phenotypes in cancer. |
Databáze: | OpenAIRE |
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