Highly Expressed FOXF1 Inhibit Non-Small-Cell Lung Cancer Growth via Inducing Tumor Suppressor and G1-Phase Cell-Cycle Arrest
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...
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doaj-080242476b3747138e6cb188dc1085d42020-11-25T03:27:14ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-05-01213227322710.3390/ijms21093227Highly Expressed FOXF1 Inhibit Non-Small-Cell Lung Cancer Growth via Inducing Tumor Suppressor and G1-Phase Cell-Cycle ArrestChia-Yu Wu0Chun-Hao Chan1Navneet Kumar Dubey2Hong-Jian Wei3Jui-Hua Lu4Chun-Chao Chang5Hsin-Chung Cheng6Keng-Liang Ou7Win-Ping Deng8Division of Oral and Maxillofacial Surgery, Department of Dentistry, Taipei Medical University Hospital, Taipei 11031, TaiwanSchool of Dentistry, College of Oral Medicine, Taipei Medical University, Taipei 11031, TaiwanSchool of Dentistry, College of Oral Medicine, Taipei Medical University, Taipei 11031, TaiwanSchool of Dentistry, College of Oral Medicine, Taipei Medical University, Taipei 11031, TaiwanSchool of Dentistry, College of Oral Medicine, Taipei Medical University, Taipei 11031, TaiwanDivision of Gastroenterology and Hepatology, Department of Internal Medicine, Taipei Medical University Hospital, Taipei 11031, TaiwanSchool of Dentistry, College of Oral Medicine, Taipei Medical University, Taipei 11031, TaiwanDepartment of Dentistry, Taipei Medical University-Shuang Ho Hospital, New Taipei City, TaiwanSchool of Dentistry, College of Oral Medicine, Taipei Medical University, Taipei 11031, TaiwanCancer 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-FOXF1<sup>H</sup> and H1299-FOXF1<sup>H</sup>, with upregulated tumor suppressor p21 and suppressed cellular cyclins, leading to cell-cycle arrest at the gap 1 (G1) phase. H441-FOXF1<sup>H</sup> and H1299-FOXF1<sup>H</sup> 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.https://www.mdpi.com/1422-0067/21/9/3227FOXF1lung cancercell migration, tumor suppressorcell cycle |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Chia-Yu Wu Chun-Hao Chan Navneet Kumar Dubey Hong-Jian Wei Jui-Hua Lu Chun-Chao Chang Hsin-Chung Cheng Keng-Liang Ou Win-Ping Deng |
spellingShingle |
Chia-Yu Wu Chun-Hao Chan Navneet Kumar Dubey Hong-Jian Wei Jui-Hua Lu Chun-Chao Chang Hsin-Chung Cheng Keng-Liang Ou Win-Ping Deng Highly Expressed FOXF1 Inhibit Non-Small-Cell Lung Cancer Growth via Inducing Tumor Suppressor and G1-Phase Cell-Cycle Arrest International Journal of Molecular Sciences FOXF1 lung cancer cell migration, tumor suppressor cell cycle |
author_facet |
Chia-Yu Wu Chun-Hao Chan Navneet Kumar Dubey Hong-Jian Wei Jui-Hua Lu Chun-Chao Chang Hsin-Chung Cheng Keng-Liang Ou Win-Ping Deng |
author_sort |
Chia-Yu Wu |
title |
Highly Expressed FOXF1 Inhibit Non-Small-Cell Lung Cancer Growth via Inducing Tumor Suppressor and G1-Phase Cell-Cycle Arrest |
title_short |
Highly Expressed FOXF1 Inhibit Non-Small-Cell Lung Cancer Growth via Inducing Tumor Suppressor and G1-Phase Cell-Cycle Arrest |
title_full |
Highly Expressed FOXF1 Inhibit Non-Small-Cell Lung Cancer Growth via Inducing Tumor Suppressor and G1-Phase Cell-Cycle Arrest |
title_fullStr |
Highly Expressed FOXF1 Inhibit Non-Small-Cell Lung Cancer Growth via Inducing Tumor Suppressor and G1-Phase Cell-Cycle Arrest |
title_full_unstemmed |
Highly Expressed FOXF1 Inhibit Non-Small-Cell Lung Cancer Growth via Inducing Tumor Suppressor and G1-Phase Cell-Cycle Arrest |
title_sort |
highly expressed foxf1 inhibit non-small-cell lung cancer growth via inducing tumor suppressor and g1-phase cell-cycle arrest |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1661-6596 1422-0067 |
publishDate |
2020-05-01 |
description |
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-FOXF1<sup>H</sup> and H1299-FOXF1<sup>H</sup>, with upregulated tumor suppressor p21 and suppressed cellular cyclins, leading to cell-cycle arrest at the gap 1 (G1) phase. H441-FOXF1<sup>H</sup> and H1299-FOXF1<sup>H</sup> 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. |
topic |
FOXF1 lung cancer cell migration, tumor suppressor cell cycle |
url |
https://www.mdpi.com/1422-0067/21/9/3227 |
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