2. Academic Validation
  3. Glioma-associated oncogene homolog 1 stimulates FOXP3 to promote non-small cell lung cancer stemness

Glioma-associated oncogene homolog 1 stimulates FOXP3 to promote non-small cell lung cancer stemness

  • Am J Transl Res. 2020 May 15;12(5):1839-1850.
Haolong Qi 1 2,  Wende Li 3,  Jie Zhang 4,  Jianxin Chen 5,  Jia Peng 2,  Yi Liu 2 6,  Shucai Yang 7,  Jing Du 8,  Xiang Long 8,  Calvin Sh Ng 2,  Ming-Yue Li 2 9 10,  George G Chen 2 6 9
Affiliations

Affiliations

  • 1 Department of Hepatobiliary Surgery, Renmin Hospital of Wuhan University Wuhan, Hubei, China.
  • 2 Department of Surgery, The Chinese University of Hong Kong, Prince of Wales Hospital Shatin, NT, Hong Kong, China.
  • 3 Guangdong Key Laboratory of Laboratory Animal, Guangdong Laboratory Animals Monitoring Institute Guangzhou, Guangdong, China.
  • 4 Department of Thyroid and Breast Surgery, Zhongnan Hospital of Wuhan University Wuhan, Hubei, China.
  • 5 Department of Surgery, Jiangxia District Hospital of Traditional Chinese Medicine Wuhan, Hubei, China.
  • 6 Guangdong Key Laboratory for Research and Development of Natural Drugs, Guangdong Medical University Zhanjiang, Guangdong, China.
  • 7 Department of Clinical Laboratory, Pingshan District People's Hospital of Shenzhen Shenzhen, Guangdong, China.
  • 8 Peking University Shenzhen Hospital Shenzhen, Guangdong, China.
  • 9 Shenzhen Research Institute, The Chinese University of Hong Kong Shenzhen, Guangdong, China.
  • 10 Guangzhou Regenerative Medicine and Health Guangdong Laboratory Guangzhou, Guangdong, China.
PMID: 32509180
Abstract

Glioma-associated oncogene homolog 1 (GLI1), an oncogenic molecule in non-small cell lung Cancer (NSCLC), promotes the growth of NSCLC by enhancing lung Cancer Stem Cells (LCSCs). However, the mechanism responsible remains unknown. FOXP3 is known to maintain LCSCs. The aim of this study was to explore whether GLI1 enhanced LCSCs via stimulating FOXP3. Experiments were performed in NSCLC tissue samples, cell lines and the animal tumor model. The expression of GLI1- and LCSC-related molecules was assessed at protein and mRNA levels. Relevant cell functions were also determined. A tumor xenograft mouse model was established to confirm the oncogenic role of GLI1. We confirmed that the expression of GLI1 was up-regulated in the tumor tissues of NSCLC compared with adjacent non-tumor tissues. But no significant association between GLI1 and clinicopathological characteristics was found. GLI1 expression was positively correlated with FOXP3 and it could promote FOXP3 expression likely via acting on the promoter of FOXP3. Along with the upregulation of FOXP3, GLI1 increased the expression of LCSC markers, ALDH1A1 and OCT4A, and the formation of tumor spheres, whereas the inhibition of GLI1 decreased the above features. We also found the involvement of Notch1 activation in GLI1-mediated FOXP3 pathway. The In vivo mouse tumor model verified the positive role of GLI1 in the growth of the tumor. Collectively, this study has demonstrated that GLI1 stimulates FOXP3 to promote LCSCs.

Keywords

FOXP3; Glioma-associated oncogene homolog 1; Notch1; cancer stem cells; lung cancer.

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