scholarly journals Asymmetric Division Gene Neurl2 Mediates Twist2 Regulation of Self-Renewal of Mouse Lewis Lung Cancer Stem Cells

2019 ◽  
Vol 10 (15) ◽  
pp. 3381-3388 ◽  
Author(s):  
Doudou Liu ◽  
H. Rosie Xing ◽  
Yongli Liu ◽  
Zhiwei Sun ◽  
Ting Ye ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Asymmetric Division ◽  
Lewis Lung ◽  
Lewis Lung Cancer ◽  
Self Renewal ◽  
Lung Cancer Stem Cells

scholarly journals Autophagy augments the self-renewal of lung cancer stem cells by the degradation of ubiquitinated p53

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Jianyu Wang ◽  
Doudou Liu ◽  
Zhiwei Sun ◽  
Ting Ye ◽  
Jingyuan Li ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Cell Lines ◽  
Human Cancer ◽  
Suppressor Activity ◽  
Self Renewal ◽  
Tumor Suppressor Activity ◽  
Lung Cancer Stem Cells ◽  
First Time

AbstractIt has been postulated that cancer stem cells (CSCs) are involved in all aspects of human cancer, although the mechanisms governing the regulation of CSC self-renewal in the cancer state remain poorly defined. In the literature, both the pro- and anti-oncogenic activities of autophagy have been demonstrated and are context-dependent. Mounting evidence has shown augmentation of CSC stemness by autophagy, yet mechanistic characterization and understanding are lacking. In the present study, by generating stable human lung CSC cell lines with the wild-type TP53 (A549), as well as cell lines in which TP53 was deleted (H1229), we show, for the first time, that autophagy augments the stemness of lung CSCs by degrading ubiquitinated p53. Furthermore, Zeb1 is required for TP53 regulation of CSC self-renewal. Moreover, TCGA data mining and analysis show that Atg5 and Zeb1 are poor prognostic markers of lung cancer. In summary, this study has elucidated a new CSC-based mechanism underlying the oncogenic activity of autophagy and the tumor suppressor activity of p53 in cancer, i.e., CSCs can exploit the autophagy-p53-Zeb1 axis for self-renewal, oncogenesis, and progression.

scholarly journals Sulforaphane Inhibits Self-renewal of Lung Cancer Stem Cells Through the Modulation of Polyhomeotic Homolog 3 and Sonic Hedgehog Signaling Pathways

2019 ◽  
Author(s):  
FanPing Wang ◽  
Jiateng Zhong ◽  
Shanshan Wang ◽  
Caijuan Qiao ◽  
Xiangyang Li ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Western Blot ◽  
Cancer Cells ◽  
Signaling Pathways ◽  
Sonic Hedgehog ◽  
Self Renewal ◽  
Shh Signaling ◽  
Lung Cancer Stem Cells

Abstract Background: Sulforaphane (SFN), an active compound in cruciferous vegetables has been characterized for its antiproliferative capacity. We investigated the role and molecular mechanism through which SFN regulates proliferation and self-renewal of lung cancer stem cells. Methods: Lung cancer stem cells (CD133-positive cells) were isolated by MACs and then measured by flow cytometry. The ability of cell proliferation was assessed by MTT assays and tumorsphere formation assays. The expressions of Sonic Hedgehog (Shh), Smoothened (Smo), Gli1 and Human Polyhomeotic Homolog 3 (PHC3) in cells were measured by quantitative reverse transcription polymerase chain reaction (qPCR) and western blot assays. The expression of transcription factor SOX2 in lung cancer stem cells was also determined by western blot assay. Shh was knocked down by siRNA to further study the role of SFN and Shh signaling pathways in lung cancer. Results: SFN inhibited the proliferation of lung cancer cells and lung cancer stem cells simultaneously. Meanwhile, we observed that Sonic Hedgehog (SHH) signaling pathway, SOX2 and Polyhomeotic Homolog 3 (PHC3) were highly activated in lung cancer stem cells. Knock-down of Shh led to reduced H460 and A549 cells proliferation. Furthermore, we observed that SFN inhibited the activity of PHC3 and SHH signaling pathways in the lung cancer stem cells. In addition, SFN combined with Knock-down of Shh gene showed a greater effect on the proliferation of lung cancer cells. Conclusion: SFN is an effective new drug which can inhibit proliferation of lung cancer stem cells through the modulation of PHC3 and SHH signaling pathways. It provides a novel target for improving therapeutic efficacy for lung cancer stem cells.

scholarly journals Sulforaphane inhibits self-renewal of lung cancer stem cells through the modulation of sonic Hedgehog signaling pathway and polyhomeotic homolog 3

AMB Express ◽  
2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Fanping Wang ◽  
Yanwei Sun ◽  
Xiaoyu Huang ◽  
Caijuan Qiao ◽  
Wenrui Zhang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Cancer Cells ◽  
Sonic Hedgehog ◽  
Hedgehog Signaling ◽  
Lung Cancer Cells ◽  
Sonic Hedgehog Signaling ◽  
Self Renewal ◽  
Lung Cancer Stem Cells

AbstractSulforaphane (SFN), an active compound in cruciferous vegetables, has been characterized by its antiproliferative capacity. We investigated the role and molecular mechanism through which SFN regulates proliferation and self-renewal of lung cancer stem cells. CD133+ cells were isolated with MACs from lung cancer A549 and H460 cells. In this study, we found that SFN inhibited the proliferation of lung cancer cells and self-renewal of lung cancer stem cells simultaneously. Meanwhile, the mRNA and protein expressions of Shh, Smo, Gli1 and PHC3 were highly activated in CD133+ lung cancer cells. Compared with siRNA-control group, Knock-down of Shh inhibited proliferation of CD133+ lung cancer cells, and decreased the protein expression of PHC3 in CD133+ lung cancer cells. Knock-down of PHC3 also affected the proliferation and decreased the Shh expression level in CD133+ lung cancer cells. In addition, SFN inhibited the activities of Shh, Smo, Gli1 and PHC3 in CD133+ lung cancer cells. Furthermore, the inhibitory effect of SFN on the proliferation of siRNA-Shh and siRNA-PHC3 cells was weaker than that on the proliferation of siRNA-control cells. Sonic Hedgehog signaling pathway might undergo a cross-talk with PHC3 in self-renewal of lung cancer stem cells. SFN might be an effective new drug which could inhibit self-renewal of lung cancer stem cells through the modulation of Sonic Hedgehog signaling pathways and PHC3. This study could provide a novel way to improve therapeutic efficacy for lung cancer stem cells.

Autophagy Augments the Self-Renewal of Lung Cancer Stem Cells by Degradation of Ubiquitinated TP53

2019 ◽  
Author(s):  
Jianyu Wang ◽  
Doudou Liu ◽  
Zhiwei Sun ◽  
Ting Ye ◽  
Jingyuan Li ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
The Self ◽  
Self Renewal ◽  
Lung Cancer Stem Cells

scholarly journals Short hairpin RNA targeting AKT1 and PI3K/p85 suppresses the proliferation and self-renewal of lung cancer stem cells

2012 ◽  
Vol 12 (1) ◽  
pp. 363-370 ◽  
Author(s):  
AI-GUI JIANG ◽  
HUI-YU LU ◽  
DE-GENG ZHANG ◽  
LI-XIN ZHANG ◽  
XIAO-YAN GAO
Keyword(s):  
Lung Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Short Hairpin Rna ◽  
Hairpin Rna ◽  
Self Renewal ◽  
Rna Targeting ◽  
Lung Cancer Stem Cells ◽  
Short Hairpin

scholarly journals Sulforaphane Inhibits Self-renewal of Lung Cancer Stem Cells Through the Modulation of Sonic Hedgehog Signaling Pathway and Polyhomeotic Homolog3

2021 ◽  
Author(s):  
FanPing Wang ◽  
Yanwei Sun ◽  
Xiaoyu Huang ◽  
Caijuan Qiao ◽  
Wenrui Zhang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Protein Expression ◽  
Cancer Cells ◽  
Signaling Pathways ◽  
Sonic Hedgehog ◽  
Self Renewal ◽  
Shh Signaling ◽  
Lung Cancer Stem Cells

Abstract Sulforaphane (SFN), an active compound in cruciferous vegetables has been characterized for its antiproliferative capacity. We investigated the role and molecular mechanism through which SFN regulates proliferation and self-renewal of lung cancer stem cells (CSCs). CD133-positive lung cancer cells were isolated by MACs from lung cancer A549 and H460 cells. And then, the expression of CD133 was measured by flow cytometry assays (FACS). The ability of cell proliferation was assessed by MTT assays and tumorsphere formation assays. The mRNA expression of Sonic Hedgehog (Shh), Smoothened (Smo), Gli1 and Human Polyhomeotic Homolog 3 (PHC3) was measured by quantitative reverse transcription polymerase chain reaction (QPCR). And the protein expression of Shh, Smo, Gli1 and PHC3 was determined by western blotting. Shh was knocked down by siRNA to further study the role of Shh signaling pathways in lung CSCs. SFN inhibited the proliferation of lung cancer cells and lung CSCs simultaneously. Meanwhile, the mRNA and protein expressions of Shh, Smo, Gli1 and PHC3 were highly activated in A549 /CD133+ and H460 /CD133+ cells. Compared with siRNA-control group, Knock-down of Shh inhibited proliferation of A549/ CD133+ and H460/ CD133+ cells, and decreased the protein expression of PHC3 in A549/ CD133+ and H460/ CD133+ cells. In addition, SFN inhibited the activities of Shh, Smo, Gli1 and PHC3 in A549/ CD133+ and H460/ CD133+ cells. Furthermore, the inhibitory effect of SFN on the proliferation of siRNA-shh cells is weaker than that of siRNA-control cells. SFN is an effective new drug which can inhibit proliferation of lung CSCs through the modulation of PHC3 and SHH signaling pathways. It provides a novel target for improving therapeutic efficacy for lung CSCs.

scholarly journals Alpha-enolase (ENO1), identified as an antigen to monoclonal antibody 12C7, promotes the self-renewal and malignant phenotype of lung cancer stem cells by AMPK/mTOR pathway

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Xiong Shu ◽  
Kai-Yue Cao ◽  
Hui-Qi Liu ◽  
Long Yu ◽  
Li-Xin Sun ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Stem Cells ◽  
Monoclonal Antibody ◽  
Cancer Stem Cells ◽  
Bioinformatics Analysis ◽  
Mtor Pathway ◽  
Rna Seq ◽  
Self Renewal ◽  
Lung Cancer Stem Cells ◽  
Anti Tumor Activity

Abstract Background Tumor-associated antigens (TAAs) can be targeted in cancer therapy. We previously identified a monoclonal antibody (mAb) 12C7, which presented anti-tumor activity in lung cancer stem cells (LCSCs). Here, we aimed to identify the target antigen for 12C7 and confirm its role in LCSCs. Methods Immunofluorescence was used for antigen localization. After targeted antigen purification by electrophoresis and immunoblot, the antigen was identified by LC-MALDI-TOF/TOF mass spectrometry, immunofluorescence, and immunoprecipitation. The overexpression or silence of ENO1 was induced by lentiviral transduction. Self-renewal, growth, and invasion of LCSCs were evaluated by sphere formation, colony formation, and invasion assay, respectively. High-throughput transcriptome sequencing (RNA-seq) and bioinformatics analysis were performed to analyze downstream targets and pathways of targeted antigen. Results Targeted antigen showed a surface antigen expression pattern, and the 43–55 kDa protein band was identified as α-enolase (ENO1). Self-renewal, growth, and invasion abilities of LCSCs were remarkably inhibited by ENO1 downregulation, while enhanced by ENO1 upregulation. RNA-seq and bioinformatics analysis eventually screened 4 self-renewal-related and 6 invasion-related differentially expressed genes. GSEA analysis and qRT-PCR verified that ENO1 regulated self-renewal, invasion-related genes, and pathways. KEGG pathway analysis and immunoblot demonstrated that ENO1 inactivated AMPK pathway and activated mTOR pathway in LCSCs. Conclusions ENO1 is identified as a targeted antigen of mAb 12C7 and plays a pivotal role in facilitating self-renewal, growth, and invasion of LCSCs. These findings provide a potent therapeutic target for the stem cell therapy for lung cancer and have potential to improve the anti-tumor activity of 12C7.

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