scholarly journals Napsin A is negatively associated with EMT‑mediated EGFR‑TKI resistance in lung cancer cells

2018 ◽  
Author(s):  
Linshui Zhou ◽  
Xin Lv ◽  
Junchao Yang ◽  
Yuanhong Zhu ◽  
Zhen Wang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Cells ◽  
Lung Cancer Cells ◽  
Negatively Associated ◽  
Napsin A ◽  
Tki Resistance ◽  
Egfr Tki

scholarly journals Targeting the miR-200c/LIN28B axis in acquired EGFR-TKI resistance non-small cell lung cancer cells harboring EMT features

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Hiroki Sato ◽  
Kazuhiko Shien ◽  
Shuta Tomida ◽  
Kazuhiro Okayasu ◽  
Ken Suzawa ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cancer Cells ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Lung Cancer Cells ◽  
Small Cell Lung ◽  
Tki Resistance ◽  
Egfr Tki

scholarly journals DDX3X mediates EGFR-TKI resistance through VEGFR signaling

2021 ◽  
Author(s):  
Aya Ohtsubo ◽  
Hiroshi Kagamu ◽  
Satoshi Watanabe ◽  
Kunihiro Shono ◽  
Takaaki Masuda ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Cells ◽  
Epithelial Mesenchymal Transition ◽  
Lung Cancer Cells ◽  
Human Lung Cancer ◽  
Antitumor Effects ◽  
Mesenchymal Transition ◽  
Tki Resistance ◽  
Egfr Tki ◽  
Egfr Tkis

Abstract Although epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) are remarkably effective against non-small-cell lung cancer (NSCLC) with EGFR-activating mutations, lung cancer cells acquire resistance to EGFR-TKIs without exception. Several mechanisms of EGFR-TKI resistance have been reported, but there are many aspects that remain to be clarified. We previously identified DDX3X as an immunogenic protein preferentially expressed in murine melanoma with a cancer stem cell (CSC)-like phenotype. DDX3X induced epithelial-mesenchymal transition and reduced the sensitivity to EGFR-TKIs in PC9 cells, human lung cancer cells harboring EGFR exon 19 deletion. We also reported that there was a small nonadherent subpopulation of parental PC9 cells that highly expressed DDX3X and had CSC properties. In this study, we found that VEGFR2 was upregulated in lung cancer cells that strongly expressed DDX3X and that these cells were addicted to VEGFR signaling. The blockade of both EGFR and VEGFR signaling reduced the phosphorylation of downstream signals in the cells with DDX3X that acquired EGFR-TKI resistance. The addition of VEGFR-TKIs or anti-VEGF antibodies to EGFR-TKIs significantly inhibited the progression of EGFR-mutated NSCLC in a xenograft mouse model. These data suggest that the blockade of VEGFR signaling enhances the antitumor effects of EGFR-TKIs by eradicating cancer stem cells, which mediate resistance to EGFR-TKIs.

scholarly journals Inhibition of miR-185-3p Confers Erlotinib Resistance Through Upregulation of PFKL/MET in Lung Cancers

2021 ◽  
Vol 9 ◽  
Author(s):  
Ke Li ◽  
Xinling Zhu ◽  
Conghu Yuan
Keyword(s):  
Lung Cancer ◽  
Cancer Cells ◽  
Kinase Inhibitor ◽  
Growth Factor Receptor ◽  
Lung Cancer Cells ◽  
Cell Counting ◽  
Luciferase Assay ◽  
Lung Cancers ◽  
Tki Resistance ◽  
Egfr Tki

Erlotinib (ER), as an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), has a significant therapeutic effect in lung cancers. However, EGFR TKI resistance inevitably occurs after treatment for approximately 12 months, which weakens its antitumor effect. Here, we identified miR-185-3p as a significantly downregulated microRNA responsible for acquired EGFR TKI resistance in cells and patients with lung cancer. qRT-PCR and Western Blot were performed to determine the relative expression of miR-185-3p in ER-resistant tumor tissues and cells. The viability and apoptosis of lung cancer cells were evaluated by Cell Counting Kit-8 (CCK8) assay and flow cytometry, respectively. The binding between miR-185-3p and liver-type phosphofructokinase (PFKL) was verified by dual luciferase assay. It was found that overexpression of miR-185-3p conferred ER sensitivity in lung cancer cell lines. MiR-185-3p was downregulated in ER-resistant lung cancer cells (H1299/ER and A549/ER). MiR-185-3p inhibited proliferation and induced cell apoptosis in ER-resistant cells. Mechanistically, miR-185-3p downregulation contributed to ER resistance through upregulating the PFKL. Moreover, Mesenchymal to epithelial transition (MET) oncoprotein promoted EGFR-TKI resistance by regulating miR-185-3p and PFKL. These findings revealed a novel mechanism in which downregulation of miR-185-3p may induce overexpression of PFKL and MET and confer ER resistance in lung cells. Combination of PFKL/MET inhibitors and EGFR TKIs could be a rational therapeutic approach for lung cancer patients with EGFR mutation.

scholarly journals DDX3X Induces Primary EGFR-TKI Resistance Based on Intratumor Heterogeneity in Lung Cancer Cells Harboring EGFR-Activating Mutations

PLoS ONE ◽  
2014 ◽  
Vol 9 (10) ◽  
pp. e111019 ◽  
Author(s):  
Koichiro Nozaki ◽  
Hiroshi Kagamu ◽  
Satoshi Shoji ◽  
Natsue Igarashi ◽  
Aya Ohtsubo ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Cells ◽  
Lung Cancer Cells ◽  
Intratumor Heterogeneity ◽  
Activating Mutations ◽  
Tki Resistance ◽  
Egfr Tki

scholarly journals P3.02b-121 Targeting miR-200c/LIN28B Axis in Acquired EGFR-TKI Resistance Non-Small Cell Lung Cancer Cells Harboring EMT Features

2017 ◽  
Vol 12 (1) ◽  
pp. S1267
Author(s):  
Kazuhiko Shien ◽  
Hiroki Sato ◽  
Ken Suzawa ◽  
Shuta Tomida ◽  
Shinsuke Hashida ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cancer Cells ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Lung Cancer Cells ◽  
Small Cell Lung ◽  
Tki Resistance ◽  
Egfr Tki

Effects and mechanisms of betulinic acid on improving EGFR TKI-resistance of lung cancer cells

2018 ◽  
Vol 33 (11) ◽  
pp. 1153-1159 ◽  
Author(s):  
Jiunn-Liang Ko ◽  
Ching-Hsiung Lin ◽  
Heng-Chung Chen ◽  
Wei-Heng Hung ◽  
Peng-Ju Chien ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Cells ◽  
Betulinic Acid ◽  
Lung Cancer Cells ◽  
Tki Resistance ◽  
Egfr Tki

scholarly journals ELF3 Is a Target That Promotes Therapeutic Efficiency in EGFR Tyrosine Kinase Inhibitor-Resistant Non-Small Cell Lung Cancer Cells via Inhibiting PKCί

2021 ◽  
Vol 22 (22) ◽  
pp. 12287
Author(s):  
Jeon-Soo Lee ◽  
Young Eun Choi ◽  
Sunshin Kim ◽  
Ji-Youn Han ◽  
Sung-Ho Goh
Keyword(s):  
Lung Cancer ◽  
Cell Death ◽  
Tyrosine Kinase ◽  
Cancer Cells ◽  
Small Cell ◽  
Lung Cancer Cells ◽  
Therapeutic Effects ◽  
Small Cell Lung ◽  
Egfr Tyrosine Kinase ◽  
Egfr Tki

(1) Background: Mutations in epidermal growth factor receptor (EGFR) proteins account for many non-small cell lung cancers (NSCLCs), and EGFR tyrosine kinase inhibitors (TKIs) are being used as targeted therapeutics. However, resistance to TKIs continues to increase owing to additional mutations in more than half of the patients receiving EGFR TKI therapy. In addition to targeting new mutations with next-generation therapeutics, it is necessary to find an alternative target to overcome the challenges associated with resistance. (2) Methods: To identify potential alternative targets in patients with NSCLC undergoing targeted therapy, putative targets were identified by transcriptome profiling and validated for their biological and therapeutic effects in vitro and in vivo. (3) Results: ELF3 was found to be differentially expressed in NSCLC, and ELF3 knockdown significantly increased cell death in K-Ras mutant as well as in EGFR L858R/T790M mutation harboring lung cancer cells. We also found that auranofin, an inhibitor of protein kinase C iota (PKCί), a protein upstream of ELF3, effectively induced cell death. (4) Conclusions: Our study suggests that blocking ELF3 is an effective way to induce cell death in NSCLC with K-Ras and EGFR T790M/L858R mutations and thus advocates the use of auranofin as an effective alternative drug to overcome EGFR TKI resistance.

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