Tailored modulation of stemness and drug resistance marker characteristics in K-Ras mutant lung cancer cells via PD-L1 gene suppression

We aimed to analyze the association of tumor cell-specific Programmed Cell Death Ligand 1 (PD-L1) expression with stemness markers and multi-drug resistance genes in non-small cell lung cancer. ATP Binding Cassette Subfamily G Member 2 (ABCG2), Aldehyde dehydrogenase 1 family, member A1 (ALDH1A1), C...

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Bibliographic Details
Published in:Life sciences (1973) 2022-12, Vol.311, p.121171-121171, Article 121171
Main Authors: Unver, Nese, Tavukcuoglu, Ece, Esendagli, Gunes
Format: Article
Language:English
Subjects:
Cancer stemness
K-Ras
Lung cancer
Multi-drug resistance
PD-L1
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Summary:We aimed to analyze the association of tumor cell-specific Programmed Cell Death Ligand 1 (PD-L1) expression with stemness markers and multi-drug resistance genes in non-small cell lung cancer. ATP Binding Cassette Subfamily G Member 2 (ABCG2), Aldehyde dehydrogenase 1 family, member A1 (ALDH1A1), CD44, Epithelial cell adhesion molecule (EPCAM), Kruppel-like factor 4 (KLF4), MYC Proto-Oncogene (MYC), Nanog Homeobox (NANOG), SRY-Box Transcription Factor 2 (SOX2) as well as ATP Binding Cassette Subfamily C Member (ABCC) 1–6, ABCC10–12 with ATP Binding Cassette Subfamily B Member (ABCB) 1 and ABCB4–9 belongs to ABC transporters family were analyzed and their correlation with PD-L1 was evaluated using Cancer Cell Line Encyclopedia and The Cancer Genome Atlas data sets. We validated potential lung cancer stemness markers harboring ABCG2, CD44, ALDH1A1 and SOX-2, which are affected as a result of siRNA-mediated suppression of PD-L1 via flow cytometry. K-Ras downstream signaling proteins as well as multidrug resistance proteins were also investigated. PD-L1 was found to be positively correlated with CD44, whereas negatively correlated with ALDH1A1 (Pearson r = 0.44, r = −0.48; respectively) in 45 K-Ras mutated NSCLC cells based on CCLE database. While ABCC5 was dominantly decreased in K-Ras mutant lung cancer cells affected by PD-L1 gene suppression, expression changes were observed in the activation of distinct signaling pathways in a cell line-dependent manner. The evaluation of markers in lung adenocarcinoma with different types of K-Ras mutations in terms of both stemness and drug resistance markers will contribute to the development of personalized immunotherapy regimens. [Display omitted] •We validated potential stemness markers harboring CD44 and ALDH1 in K-Ras mutated lung cancer cells with PD-L1 suppression.•PD-L1 was positively correlated with CD44, whereas negatively correlated with ALDH1 in NSCLC cells with K-Ras mutation.•The expression of ABCC5 & ABCC10 was reduced with PD-L1 repression in cell line-dependent characteristics.•K-Ras-related signaling proteins, Akt, ERK, and STAT3 showed distinct expression via modulation of PD-L1 expression.
ISSN:0024-3205
1879-0631
DOI:10.1016/j.lfs.2022.121171