ROLE OF QUIESCENCE CANCER STEM CELLS IN THE GEFITINIB RESISTANCE IN EGFR MUTATION-POSITIVE NON-SMALL CELL LUNG CANCER

Respirology ◽  
2017 ◽  
Vol 22 ◽  
pp. 18-19
Keyword(s):  
Lung Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Egfr Mutation ◽  
Small Cell ◽  
Small Cell Lung ◽  
Gefitinib Resistance

scholarly journals Role of FBXW7 in the quiescence of gefitinib-resistant lung cancer stem cells in EGFR-mutant non-small cell lung cancer

2019 ◽  
Author(s):  
Moulid Hidayat ◽  
Yoichiro Mitsuishi ◽  
Fumiyuki Takahashi ◽  
Ken Tajima ◽  
Toshifumi Yae ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
G1 Phase ◽  
Small Cell Lung ◽  
Egfr Mutant

Several recent studies suggest that cancer stem cells (CSCs) are involved in intrinsic resistance to cancer treatment. Maintenance of quiescence is crucial for establishing resistance of CSCs to cancer therapeutics. F-box/WD repeat-containing protein 7 (FBXW7) is a ubiquitin ligase that regulates quiescence by targeting the c-MYC protein for ubiquitination. We previously reported that gefitinib-resistant persisters (GRPs) in EGFR-mutant non-small cell lung cancer (NSCLC) cells highly expressed octamer-binding transcription factor 4 (Oct-4) as well as the lung CSC marker CD133, and they exhibited distinctive features of the CSC phenotype. However, the role of FBXW7 in lung CSCs and their resistance to epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors in NSCLC is not fully understood. In this study, we developed GRPs from the two NSCLC cell lines PC9 and HCC827, which express an EGFR exon 19 deletion mutation, by treatment with a high concentration of gefitinib. The GRPs from both PC9 and HCC827 cells expressed high levels of CD133 and FBXW7, but low levels of c-MYC. Cell cycle analysis demonstrated that the majority of GRPs existed in the G0/G1 phase. Knockdown of the FBXW7 gene significantly reduced the cell number of CD133-positive GRPs and reversed the cell population in the G0/G1-phase. We also found that FBXW7 expression in CD133-positive cells was increased and c-MYC expression was decreased in gefitinib-resistant tumors of PC9 cells in mice and in 9 out of 14 tumor specimens from EGFR-mutant NSCLC patients with acquired resistance to gefitinib. These findings suggest that FBXW7 plays a pivotal role in the maintenance of quiescence in gefitinib-resistant lung CSCs in EGFR mutation-positive NSCLC.

Abstract B15: miR-10a regulation of cancer stem cells in non-small cell lung cancer

2013 ◽  
Author(s):  
Chris G. Desevo ◽  
Chunli Shao ◽  
Jill Larsen ◽  
Carmen Behrens ◽  
Ignacio I. Wistuba ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung

Abstract 1975: Disulfiram targets hypoxia-induced cancer stem cells and reverses chemoresistance in non-small cell lung cancer

2018 ◽  
Author(s):  
Kate Butcher ◽  
Vinodh Kannappan ◽  
Karim Azar ◽  
Rajagopal Kilari ◽  
Ogechi Nkeonye ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung

Radioresistance of Non-small Cell Lung Cancer Stem Cells

2009 ◽  
Vol 75 (3) ◽  
pp. S542-S543 ◽  
Author(s):  
S.D. Parikh ◽  
V. Levina ◽  
T. Wang ◽  
M.K. Gibson ◽  
A.E. Lokshin
Keyword(s):  
Lung Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung ◽  
Lung Cancer Stem Cells

The effects and mechanisms of SLC34A2 on tumorigenicity in human non-small cell lung cancer stem cells

Tumor Biology ◽  
2016 ◽  
Vol 37 (8) ◽  
pp. 10383-10392 ◽  
Author(s):  
Zhanxin Jiang ◽  
Yanhong Hao ◽  
Xiaoquan Ding ◽  
Zhibin Zhang ◽  
Peng Liu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung ◽  
Lung Cancer Stem Cells

scholarly journals New Perspectives in Different Gene Expression Profiles for Early and Locally Advanced Non-Small Cell Lung Cancer Stem Cells

2021 ◽  
Vol 11 ◽  
Author(s):  
Valentina Masciale ◽  
Federico Banchelli ◽  
Giulia Grisendi ◽  
Roberto D’Amico ◽  
Antonino Maiorana ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Early Stage ◽  
Locally Advanced ◽  
Small Cell ◽  
Small Cell Lung ◽  
Advanced Stages

IntroductionLung cancer is one of the most common cancers in the world, causing over 1.7 million deaths in 2018. Thus far, no effective treatments against lung cancer for advanced stages have been found. For early stages, although surgery is considered the gold standard treatment, 30–55% of patients develop recurrence within the first 5 years of surgery. Our aim is to assess whether cancer stem cells (CSC) display overexpression of a pool of genes that were previously identified for adenocarcinoma recurrence in patients with early and locally advanced stages of non-small cell lung cancer (NSCLC).MethodsThis cross-sectional study was carried out by harvesting surgical tumor specimens obtained from patients harboring early (I-II) and locally advanced (IIIA) stages of NSCLC. For each patient, cell sorting was performed to identify and isolate the ALDHhigh (CSC) and ALDHlow (cancer cells) populations. The mRNA expressions of 31 recurrence-related genes (target genes) in both ALDHhigh and ALDHlow populations were then assessed and compared.ResultsSurgical specimens were obtained from 22 patients harboring NSCLC. Sixteen (51.6%) out of 31 recurrence-related genes were significantly overexpressed in ALDHhigh cells in the early stages and 9 (29.0%) were overexpressed in the locally advanced stages of NSCLC. Overall, the relative mRNA expressions for these recurrence-related genes were higher in early-stage patients. The average fold change, considering all 31 recurrence-related genes together, was 4.5 (95% CI = 3.1-6.3) in early-stage patients and 1.6 (95% CI = 1.2-2.2) in locally advanced-stage patients.ConclusionsOur study represents the first attempt toward identifying genes associated with recurrence that are overexpressed in cancer stem cells in patients with early and locally advanced stages of NSCLC. This finding may contribute to the identification of new target therapies tailored for NSCLC stages.

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