Highly Expressed FOXF1 Inhibit Non-Small-Cell Lung Cancer Growth via Inducing Tumor Suppressor and G1-Phase Cell-Cycle Arrest
Open Access
- 1 May 2020
- journal article
- research article
- Published by MDPI AG in International Journal of Molecular Sciences
- Vol. 21 (9), 3227
- https://doi.org/10.3390/ijms21093227
Abstract
Cancer pathogenesis results from genetic alteration-induced high or low transcriptional programs, which become highly dependent on regulators of gene expression. However, their role in progressive regulation of non-small-cell lung cancer (NSCLC) and how these dependencies may offer opportunities for novel therapeutic options remain to be understood. Previously, we identified forkhead box F1 (FOXF1) as a reprogramming mediator which leads to stemnesss when mesenchymal stem cells fuse with lung cancer cells, and we now examine its effect on lung cancer through establishing lowly and highly expressing FOXF1 NSCLC engineered cell lines. Higher expression of FOXF1 was enabled in cell lines through lentiviral transduction, and their viability, proliferation, and anchorage-dependent growth was assessed. Flow cytometry and Western blot were used to analyze cellular percentage in cell-cycle phases and levels of cellular cyclins, respectively. In mice, tumorigenic behavior of FOXF1 was investigated. We found that FOXF1 was downregulated in lung cancer tissues and cancer cell lines. Cell proliferation and ability of migration, anchorage-independent growth, and transformation were inhibited in H441-FOXF1H and H1299-FOXF1H, with upregulated tumor suppressor p21 and suppressed cellular cyclins, leading to cell-cycle arrest at the gap 1 (G1) phase. H441-FOXF1H and H1299-FOXF1H injected mice showed reduced tumor size. Conclusively, highly expressing FOXF1 inhibited NSCLC growth via activating tumor suppressor p21 and G1 cell-cycle arrest, thus offering a potentially novel therapeutic strategy for lung cancer.Funding Information
- Ministry of Science and Technology, Taiwan ((MOST 104-2313-B-038-001, 104-2221-E-038-016, 105-2314-B-038-011 and 106-2314-B-038-077-MY2))
This publication has 63 references indexed in Scilit:
- Epigenetic Inactivation of the Potential Tumor Suppressor Gene FOXF1 in Breast CancerCancer Research, 2010
- Extracellular Protease ADAMTS9 Suppresses Esophageal and Nasopharyngeal Carcinoma Tumor Formation by Inhibiting AngiogenesisCancer Research, 2010
- Genomic and Genic Deletions of the FOX Gene Cluster on 16q24.1 and Inactivating Mutations of FOXF1 Cause Alveolar Capillary Dysplasia and Other MalformationsAmerican Journal of Human Genetics, 2009
- Anchorage-independent cell growth signature identifies tumors with metastatic potentialOncogene, 2009
- p21 in cancer: intricate networks and multiple activitiesNature Reviews Cancer, 2009
- FoxF1 and FoxL1 Link Hedgehog Signaling and the Control of Epithelial Proliferation in the Developing Stomach and IntestineOnline Journal of Public Health Informatics, 2009
- Selection of DDX5 as a novel internal control for Q-RT-PCR from microarray data using a block bootstrap re-sampling schemeBMC Genomics, 2007
- Global gene expression profiling of PAX‐FKHR fusion‐positive alveolar and PAX‐FKHR fusion‐negative embryonal rhabdomyosarcomasThe Journal of Pathology, 2007
- Cell adhesion and signalling by cadherins and Ig-CAMs in cancerNature Reviews Cancer, 2004
- Gene-expression profiles predict survival of patients with lung adenocarcinomaNature Medicine, 2002