Epidermal growth factor receptor status and Notch inhibition in non-small cell lung cancer cells

Giannopoulou, Efstathia; Nikolakopoulos, Achilleas; Kotsirilou, D.; Lampropoulou, Angeliki; Raftopoulou, Sofia; Papadimitriou, Evangelia; Theocharis, Achilleas D.; Makatsoris, Thomas; Fasseas, Konstantinos; Kalofonos, Haralabos P.

doi:10.1186/s12929-015-0196-1

Cited by 18 publications

(24 citation statements)

References 40 publications

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“…In cancer studies, the Notch pathway has been shown to require active signals from the ERK/MAP kinase pathway downstream of Ras 37 . Moreover EGFR protein levels differentially affected Notch signaling in many lung cancer cell lines 38 . In our study, Notch inhibition significantly reduced FSK-induced proliferation of ADPKD cells and also showed some inhibitory effects on EGF-induced proliferation.…”

Section: Discussionmentioning

confidence: 99%

Aberrant Regulation of Notch3 Signaling Pathway in Polycystic Kidney Disease

Idowu

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Patel

et al. 2018

Sci Rep

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Polycystic kidney disease (PKD) is a genetic disorder characterized by fluid-filled cysts in the kidney and liver that ultimately leads to end-stage renal disease. Currently there is no globally approved therapy for PKD. The Notch signaling pathway regulates cellular processes such as proliferation and de-differentiation, which are cellular hallmarks of PKD. Thus we hypothesized that the Notch pathway plays a critical role in PKD. Evaluation of protein expression of Notch signaling components in kidneys of Autosomal Recessive PKD (ARPKD) and Autosomal Dominant PKD (ADPKD) mouse models and of ADPKD patients revealed that Notch pathway members, particularly Notch3, were consistently upregulated or activated in cyst-lining epithelial cells. Notch3 expression correlated with rapidly growing cysts and co-localized with the proliferation marker, PCNA. Importantly, Notch inhibition significantly decreased forskolin-induced Notch3 activation and proliferation of primary human ADPKD cells, and significantly reduced cyst formation and growth of human ADPKD cells cultured in collagen gels. Thus our data indicate that Notch3 is aberrantly activated and facilitates epithelial cell proliferation in PKD, and that inhibition of Notch signaling may prevent cyst formation and growth.

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Section: Discussionmentioning

confidence: 99%

Aberrant Regulation of Notch3 Signaling Pathway in Polycystic Kidney Disease

Idowu

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Patel

et al. 2018

Sci Rep

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“…Other studies have shown that there is a differential response to GSI treatment depending on the EGFR status. NSCLC cell lines with undetectable EGFR protein levels are more sensitive to GSI treatment since both autophagic and apoptotic machineries are activated ( 132 ). EGFR T790M TKI-resistant NSCLC frequently has high IGF-1R expression levels.…”

Section: Notch-related Resistance To Targeted Therapiesmentioning

confidence: 99%

“…Despite being one of the least potent GSIs in preclinical studies ( 155 ), DAPT has proven to be efficacious as single agent in treating NSCLC with altered NOTCH signaling pathway members ( 74 ), in inducing apoptosis and autophagy, preferentially in cells expressing EGFR wild type or without EGFR expression ( 132 ), by inducing cell cycle arrest in G1 and G2/M phases ( 98 ), and reducing the ALDH+ stem cell population ( 156 ). In addition, DAPT can enhance the effects of cisplatin by reducing the CD133+ stem cell subpopulation ( 157 ).…”

Section: Notch Targeting In Nsclcmentioning

confidence: 99%

Drug Resistance in Non-Small Cell Lung Cancer: A Potential for NOTCH Targeting?

et al. 2018

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Drug resistance is a major cause for therapeutic failure in non-small cell lung cancer (NSCLC) leading to tumor recurrence and disease progression. Cell intrinsic mechanisms of resistance include changes in the expression of drug transporters, activation of pro-survival, and anti-apoptotic pathways, as well as non-intrinsic influences of the tumor microenvironment. It has become evident that tumors are composed of a heterogeneous population of cells with different genetic, epigenetic, and phenotypic characteristics that result in diverse responses to therapy, and underlies the emergence of resistant clones. This tumor heterogeneity is driven by subpopulations of tumor cells termed cancer stem cells (CSCs) that have tumor-initiating capabilities, are highly self-renewing, and retain the ability for multi-lineage differentiation. CSCs have been identified in NSCLC and have been associated with chemo- and radiotherapy resistance. Stem cell pathways are frequently deregulated in cancer and are implicated in recurrence after treatment. Here, we focus on the NOTCH signaling pathway, which has a role in stem cell maintenance in non-squamous non-small lung cancer, and we critically assess the potential for targeting the NOTCH pathway to overcome resistance to chemotherapeutic and targeted agents using both preclinical and clinical evidence.

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“…Lung cancer comprises malignant lung tumors characterized by uncontrolled cell growth (24). NSCLC is the primary type of lung cancer and accounts for ~85% of all lung cancer cases (25).…”

Section: Discussionmentioning

confidence: 99%

PTEN inhibits non‑small cell lung cancer cell growth by promoting G0/G1 arrest and cell apoptosis

Liu

Huang

et al. 2018

Oncol Lett

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Non-small cell lung cancer (NSCLC) is a major type of human lung cancer and the primary cause of cancer-associated cases of mortality worldwide. Phosphatase and tensin homolog (PTEN) is a potent tumor suppressor gene in various human cancer types. The aim of the current study was to explore the role of PTEN and its associated regulatory mechanisms in NSCLC. Firstly, the expression of PTEN was detected using western blotting in a variety of NSCLC cell lines. The results revealed that compared with normal control cells, PTEN levels were significantly decreased in NSCLC cell lines (P<0.01). Short hairpin (sh)RNAs specific to PTEN were also used to knockdown endogenous PTEN in NSCLC cells. The results indicated that cell viability was significantly increased in PTEN-knockdown cells compared with those transfected with negative control shRNA (P<0.01). Conversely, overexpression of PTEN in A549 and SK-MES-1 cells significantly decreased the optical density of NSCLC cells (P<0.01). Flow cytometry was used to investigate the cell cycle; the results revealed that PTEN knockdown significantly increased the percentage of cells at G 0 /G 1 phase (P<0.01) and decreased the number of cells at S phase (P<0.01). The molecular mechanism was further explored using western blotting and the results demonstrated that PTEN overexpression increased the levels of cleaved caspase-3 (P<0.01). These results suggest that PTEN may be a potential target gene for gene therapy in patients with NSCLCs.

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Epidermal growth factor receptor status and Notch inhibition in non-small cell lung cancer cells

Cited by 18 publications

References 40 publications

Aberrant Regulation of Notch3 Signaling Pathway in Polycystic Kidney Disease

Aberrant Regulation of Notch3 Signaling Pathway in Polycystic Kidney Disease

Drug Resistance in Non-Small Cell Lung Cancer: A Potential for NOTCH Targeting?

PTEN inhibits non‑small cell lung cancer cell growth by promoting G0/G1 arrest and cell apoptosis

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