FOXF1 mediates mesenchymal stem cell fusion-induced reprogramming of lung cancer cells
Journal
Oncotarget
Journal Volume
5
Journal Issue
19
Pages
9514-9529
Date Issued
2014
Author(s)
Wei H.-J.
Nickoloff J.A.
Chen W.-H.
Liu H.-Y.
Lo W.-C.
Chang Y.-T.
Wu C.-W.
Williams D.F.
Gelovani J.G.
Deng W.-P.
Abstract
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.
Subjects
Cell fusion; FOXF1; Lung cancer cell; Mesenchymal stem cell; P21; Reprogramming
SDGs
Other Subjects
Article; cancer cell; carcinogenicity; cell fusion; cell growth; cell population; cell proliferation; cell renewal; cell structure; cell transdifferentiation; chromosome number; chromosome segregation; controlled study; diploidy; DNA content; down regulation; epithelial mesenchymal transition; FOXF1 gene; gene expression; growth inhibition; human; human cell; karyotype; lung cancer; mesenchymal stem cell; oncogene; upregulation; animal; biosynthesis; cell fusion; cytology; female; genetics; lung tumor; mesenchymal stroma cell; metabolism; mouse; multicellular spheroid; nuclear reprogramming; pathology; RNA interference; SCID mouse; tumor cell culture; tumor microenvironment; cyclin dependent kinase inhibitor 1A; forkhead transcription factor; FOXF1 protein, human; small interfering RNA; Animals; Cell Fusion; Cell Proliferation; Cell Transdifferentiation; Cellular Reprogramming; Cyclin-Dependent Kinase Inhibitor p21; Female; Forkhead Transcription Factors; Humans; Lung Neoplasms; Mesenchymal Stromal Cells; Mice; Mice, SCID; RNA Interference; RNA, Small Interfering; Spheroids, Cellular; Tumor Cells, Cultured; Tumor Microenvironment
Publisher
Impact Journals LLC
Type
journal article