Role of tyrosine kinase-independent phosphorylation of EGFR with activating mutation in cisplatin-treated lung cancer cells

(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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Attenuating role of withaferin A in the proliferation and migration of lung cancer cells via a p53‑miR‑27a/miR‑10b pathway

Oncology Letters ◽

10.3892/ol.2021.12493 ◽

2021 ◽

Vol 21 (3) ◽

Author(s):

Chen-Chu Lin ◽

Tsung-Ying Yang ◽

Hseuh-Ju Lu ◽

Chen-Kai Wan ◽

Shih-Lan Hsu ◽

...

Keyword(s):

Lung Cancer ◽

Cancer Cells ◽

Lung Cancer Cells ◽

Withaferin A ◽

And Migration ◽

Proliferation And Migration

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Role of metallothionein1h in cisplatin resistance of non-small cell lung cancer cells

Chinese Journal of Cancer Research ◽

10.1007/s11670-009-0247-9 ◽

2009 ◽

Vol 21 (4) ◽

pp. 247-254 ◽

Cited By ~ 4

Author(s):

Xin-fang Hou ◽

Qing-xia Fan ◽

Liu-xing Wang ◽

Shi-xin Lu

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cancer Cells ◽

Cell Lung Cancer ◽

Cisplatin Resistance ◽

Small Cell ◽

Lung Cancer Cells ◽

Small Cell Lung

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Glutamine Addiction and Therapeutic Strategies in Lung Cancer

International Journal of Molecular Sciences ◽

10.3390/ijms20020252 ◽

2019 ◽

Vol 20 (2) ◽

pp. 252 ◽

Cited By ~ 14

Author(s):

Karolien Vanhove ◽

Elien Derveaux ◽

Geert-Jan Graulus ◽

Liesbet Mesotten ◽

Michiel Thomeer ◽

...

Keyword(s):

Lung Cancer ◽

Cancer Cells ◽

Tricarboxylic Acid Cycle ◽

Treatment Options ◽

Redox Homeostasis ◽

Glutamine Metabolism ◽

Lung Cancer Cells ◽

Production Networks ◽

Tricarboxylic Acid Cycle Intermediates

Lung cancer cells are well-documented to rewire their metabolism and energy production networks to support rapid survival and proliferation. This metabolic reorganization has been recognized as a hallmark of cancer. The increased uptake of glucose and the increased activity of the glycolytic pathway have been extensively described. However, over the past years, increasing evidence has shown that lung cancer cells also require glutamine to fulfill their metabolic needs. As a nitrogen source, glutamine contributes directly (or indirectly upon conversion to glutamate) to many anabolic processes in cancer, such as the biosynthesis of amino acids, nucleobases, and hexosamines. It plays also an important role in the redox homeostasis, and last but not least, upon conversion to α-ketoglutarate, glutamine is an energy and anaplerotic carbon source that replenishes tricarboxylic acid cycle intermediates. The latter is generally indicated as glutaminolysis. In this review, we explore the role of glutamine metabolism in lung cancer. Because lung cancer is the leading cause of cancer death with limited curative treatment options, we focus on the potential therapeutic approaches targeting the glutamine metabolism in cancer.

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