FOXF1 mediates mesenchymal stem cell fusion-induced reprogramming of lung cancer cells

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.

A Crispr Knockout Screen Identifies Foxf1 as a Suppressor of Colorectal Cancer Metastasis that Acts through Reduced mTOR Signalling

“…Table 4). Identification of negative association between FOXF1 and RB/E2F signalling (26) and positive association with epithelial-mesenchymal transition confirmed previous reports (27), but the potential relationship between high FOXF1 and inhibition of mTOR signalling is novel and has not been shown previously.…”

Tumor cell expression of CD163 is associated to postoperative radiotherapy and poor prognosis in patients with breast cancer treated with breast-conserving surgery

“…This phenomenon is a more efficient mechanism of DNA-exchange and cellular reprogramming than the accumulation of mutations in single cells (Bastida-Ruiz et al 2016; Dittmar et al 2013; Duelli and Lazebnik 2003). Growing in vitro (Busund et al 2002, 2003; Shabo et al 2015; Wei et al 2014), in vivo (Powell et al 2011; Silk et al 2013), and clinical (LaBerge et al 2017; Lazova et al 2013; Yilmaz et al 2005) data indicate that this process occurs in solid tumors and may play a significant role in clinical tumor progression. Moreover, this process generates malignant cell clones (hybrids) with reduced susceptibility to oncological treatments (Carloni et al 2013; Nagler et al 2011; Wang et al 2012; Yang et al 2010).…”

Human-derived normal mesenchymal stem/stromal cells in anticancer therapies

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