FOXF1 mediates mesenchymal stem cell fusion-induced reprogramming of lung cancer cells.
FOXF1 mediates mesenchymal stem cell fusion-induced reprogramming of lung cancer cells.
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DOI：
10.18632/oncotarget.2413
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发表时间：
2014-10-15
期刊：
影响因子：
--
通讯作者：
Deng WP
中科院分区：
文献类型：
--
作者：
Wei HJ;Nickoloff JA;Chen WH;Liu HY;Lo WC;Chang YT;Yang PC;Wu CW;Williams DF;Gelovani JG;Deng WP
一些报告表明，恶性细胞通过与肿瘤微环境中的各种类型的基质细胞融合产生表型多样性。间充质干细胞（Mesenchymal stem cell，MSC）是肿瘤微环境的重要组成部分，是一种有前途的融合细胞，但MSC与肿瘤细胞融合的功能尚未完全阐明。在这里，我们证明了MSC与肺癌细胞自发融合，后者被重新编程为缓慢生长和干细胞样状态。转录组图谱显示，肺癌细胞在MSC融合后被重编程为更良性的状态。我们进一步鉴定了FOXF1作为重编程介体，其不仅有助于向干细胞重编程，而且有助于融合后代中p21调节的生长抑制。总的来说，MSC融合不会增强肺癌细胞的内在恶性度。MSC融合诱导的重编程对肺癌细胞的抗恶性作用是通过补充致瘤缺陷来实现的，包括恢复p21功能和正常的终末分化途径以及上调FOXF1（一种假定的肿瘤抑制因子）。这种融合过程提高了MSC融合可用于逆转癌症中的细胞表型的治疗潜力。
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.
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DOI：
10.1038/nrm2718
发表时间：
2009-07
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
通讯作者：
--
影响因子：
11.2
作者：
Liu S;Ginestier C;Ou SJ;Clouthier SG;Patel SH;Monville F;Korkaya H;Heath A;Dutcher J;Kleer CG;Jung Y;Dontu G;Taichman R;Wicha MS
通讯作者：
Wicha MS
影响因子：
14
作者：
Chen, Wei-Hong;Zeng, Rong;Deng, Win-Ping
通讯作者：
Deng, Win-Ping
影响因子：
11.5
作者：
Hung, SC;Deng, WP;Gelovani, JG
通讯作者：
Gelovani, JG
影响因子：
6.4
作者：
Busund, LTR;Killie, MK;Seljelid, R
通讯作者：
Seljelid, R