Cx32 mediates norepinephrine‐promoted EGFR‐TKI resistance in a gap junction‐independent manner in non‐small‐cell lung cancer

2019 ◽  
Vol 234 (12) ◽  
pp. 23146-23159 ◽  
Author(s):  
Jie Xie ◽  
Xiyan Wang ◽  
Hui Ge ◽  
Fuhua Peng ◽  
Ningze Zheng ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Gap Junction ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung ◽  
Independent Manner ◽  
Tki Resistance ◽  
Egfr Tki

scholarly journals Downregulation of miR-506-3p Facilitates EGFR-TKI Resistance through Induction of Sonic Hedgehog Signaling in Non-Small-Cell Lung Cancer Cell Lines

2020 ◽  
Vol 21 (23) ◽  
pp. 9307
Author(s):  
Inamul Haque ◽  
Hameem I. Kawsar ◽  
Hannah Motes ◽  
Mukut Sharma ◽  
Snigdha Banerjee ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Sonic Hedgehog ◽  
Cell Lung Cancer ◽  
Molecular Mechanisms ◽  
Small Cell ◽  
Small Cell Lung ◽  
Mesenchymal Transition ◽  
Tki Resistance ◽  
Egfr Tki

Non-small-cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutation eventually develop resistance to EGFR-targeted tyrosine kinase inhibitors (TKIs). Treatment resistance remains the primary obstacle to the successful treatment of NSCLC. Although drug resistance mechanisms have been studied extensively in NSCLC, the regulation of these mechanisms has not been completely understood. Recently, increasing numbers of microRNAs (miRNAs) are implicated in EGFR-TKI resistance, indicating that miRNAs may serve as novel targets and may hold promise as predictive biomarkers for anti-EGFR therapy. MicroRNA-506 (miR-506) has been identified as a tumor suppressor in many cancers, including lung cancer; however, the role of miR-506 in lung cancer chemoresistance has not yet been addressed. Here we report that miR-506-3p expression was markedly reduced in erlotinib-resistant (ER) cells. We identified Sonic Hedgehog (SHH) as a novel target of miR-506-3p, aberrantly activated in ER cells. The ectopic overexpression of miR-506-3p in ER cells downregulates SHH signaling, increases E-cadherin expression, and inhibits the expression of vimentin, thus counteracting the epithelial–mesenchymal transition (EMT)-mediated chemoresistance. Our results advanced our understanding of the molecular mechanisms underlying EGFR-TKI resistance and indicated that the miR-506/SHH axis might represent a novel therapeutic target for future EGFR mutated lung cancer treatment.

scholarly journals Apatinib combined with EGFR-TKI in treating advanced non-small cell lung cancer with EGFR-TKI resistance

2019 ◽  
Vol 30 ◽  
pp. v625-v626
Author(s):  
R. Tian ◽  
W. Guo ◽  
Y. Guo ◽  
X. Zhang ◽  
H. Zhu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung ◽  
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 Lymecycline reverses acquired EGFR-TKI resistance in non–small-cell lung cancer by targeting GRB2

2020 ◽  
Vol 159 ◽  
pp. 105007 ◽  
Author(s):  
Yang Chen ◽  
Jie Wu ◽  
Hongfei Yan ◽  
Yang Cheng ◽  
Yizhe Wang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung ◽  
Tki Resistance ◽  
Egfr Tki

Effect of metformin on the effects of TKI on human lung carcinoma cells harboring KRAS or EGFR-T790M mutation.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e18051-e18051
Author(s):  
Yongsheng Wang ◽  
Yu Ma ◽  
Dan Li ◽  
Fuchun Guo
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Dependent Manner ◽  
Small Cell Lung ◽  
T790m Mutation ◽  
Tki Resistance ◽  
Egfr Tki ◽  
Egfr T790m

e18051 Background: K-ras and egfr-T790M mutation show primary and acquired resistance to EGFR-TKI in non-small cell lung cancer, respectively. The antidiabetic drug metformin has been associated with a decreased incidence and a better prognosis of lung cancer. The affects of metformin on the EGFR-TKI resistance in non-small cell lung cancer remain unknown. Methods: The effects of metformin on EGFR-TKI were investigated in k-ras mutant A549 cells, and egfr-T790M mutant H1975 cells both in virto and in vivo. The proliferation and apoptosis were tested. The underlying mechanisms were also analyzed. Results: Our data showed metformin significantly enhanced the inhibition activity of gefitinib both in A549 and H1975 cells in vitro. At the molecular level, metformin inhibited multiple signaling including LKB1-AMPK-S6K, PI3K-AKT and Raf-MEK-MAPK in a dose-dependent manner. Furthermore, the increased tumor inhibitions were observed in nude mice models of A549 (P<0.05)and H1975 (P<0.01). Conclusions: Metformin can increase the effects of EGFR-TKI in lung adenocarcinoma harboring K-ras and egfr-T790M mutation. Our study may provide a new strategy to overcome the EGFR-TKI resistance in NSCLC.

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