Investigation of neurotrophic tyrosine kinase receptor 1 fusions and neurotrophic tyrosine kinase receptor family expression in non-small-cell lung cancer and sensitivity to AZD7451 in vitro

Tatematsu, Tsutomu; Sasaki, Hidefumi; Shimizu, Shigeki; Okuda, Kunio; Shitara, Masayuki; Hikosaka, Yu; Moriyama, Satoru; Yano, Motoki; Brown, Jeffrey L.; Fujii, Yoshitaka

doi:10.3892/mco.2014.318

Cited by 28 publications

(27 citation statements)

References 8 publications

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“…Fourteen SCLC cell lines (SBC3, SBC5, LCMA, Lu135, N417, H2081, H146, Lu139, Lu130, H69, H446, H526, H889, and H510A), seven adenocarcinoma cell lines (A549, ABC1, LC‐2/ad, VMRC‐LCD, H292, H441, and H1651), one adenosquamous cell carcinoma cell line (H596), and one large‐cell carcinoma (H460) were used for Western blot and/or gene expression analyses per mRNA‐Seq. H460, derived as a large‐cell carcinoma, has been regarded as a LCNEC cell line in some studies . The 14 SCLC cell lines and H460 cell line are described as 15 high‐grade neuroendocrine tumor cell lines in the present study for convenience.…”

Section: Methodsmentioning

confidence: 98%

Loss of YAP1 defines neuroendocrine differentiation of lung tumors

et al. 2016

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YAP1, the main Hippo pathway effector, is a potent oncogene and is overexpressed in non‐small‐cell lung cancer (NSCLC); however, the YAP1 expression pattern in small‐cell lung cancer (SCLC) has not yet been elucidated in detail. We report that the loss of YAP1 is a special feature of high‐grade neuroendocrine lung tumors. A hierarchical cluster analysis of 15 high‐grade neuroendocrine tumor cell lines containing 14 SCLC cell lines that depended on the genes of Hippo pathway molecules and neuroendocrine markers clearly classified these lines into two groups: the YAP1‐negative and neuroendocrine marker‐positive group (n = 11), and the YAP1‐positive and neuroendocrine marker‐negative group (n = 4). Among the 41 NSCLC cell lines examined, the loss of YAP1 was only observed in one cell line showing the strong expression of neuroendocrine markers. Immunostaining for YAP1, using the sections of 189 NSCLC, 41 SCLC, and 30 large cell neuroendocrine carcinoma (LCNEC) cases, revealed that the loss of YAP1 was common in SCLC (40/41, 98%) and LCNEC (18/30, 60%), but was rare in NSCLC (6/189, 3%). Among the SCLC and LCNEC cases tested, the loss of YAP1 correlated with the expression of neuroendocrine markers, and a survival analysis revealed that YAP1‐negative cases were more chemosensitive than YAP1‐positive cases. Chemosensitivity test for cisplatin using YAP1‐positive/YAP1‐negative SCLC cell lines also showed compatible results. YAP1‐sh‐mediated knockdown induced the neuroendocrine marker RAB3a, which suggested the possible involvement of YAP1 in the regulation of neuroendocrine differentiation. Thus, we showed that the loss of YAP1 has potential as a clinical marker for predicting neuroendocrine features and chemosensitivity.

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Section: Methodsmentioning

confidence: 98%

Loss of YAP1 defines neuroendocrine differentiation of lung tumors

et al. 2016

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“…There is a close association between smoking and lung carcinoma; in addition, atmospheric pollution and automobile exhaust fumes are also lung cancer risk factors. Furthermore, chronic bronchitis, pulmonary heart disease, pulmonary fibrosis, pulmonary tuberculosis and pneumoconiosis are associated with the incidence of lung cancer (3,4).…”

Section: Introductionmentioning

confidence: 99%

Genistein inhibits A549 human lung cancer cell proliferation via miR-27a and MET signaling

et al. 2016

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Abstract. Genistein is a soybean isoflavone; in its aglycone it has various biological activities. Animal experiments, clinical studies and epidemiological investigations suggest that genistein has preventative and curative functions for a number of diseases, particularly in cancer. The present study explored the potential anti-cancer effect of genistein by observing its role in inhibiting A549 human lung cancer cell proliferation and investigating the possible mechanism. A549 cells were exposed to various concentrations of genistein (0, 10, 25, 50, 100 and 200 µM; dissolved in physiological saline) for 1, 2 and 3 days. Subsequently, the viability of A549 cells was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, cell apoptosis was examined using a flow cytometer, caspase 3/9 activity was measured using commercial kits, reverse transcription quantitative polymerase chain reaction was used to analyze the miR-27a expression and western blotting was used to investigate MET protein expression. The results suggested a significant inhibition of A549 cell growth following treatment with genistein in a time-and dose-dependent manner. The current study also indicated that treatment with genistein significantly induces cell apoptosis and promotes caspase-3/9 activation of A549 cells in a dose-dependent manner. Further functional assays revealed that the anti-cancer effect of genistein activated microRNA-27a (miR-27a) expression levels and reduced MET protein expression in A549 cells. In conclusion, the present study demonstrates that genistein inhibits A549 human lung cancer cell proliferation. Furthermore, this study reports, for the first time, a correlation between the anti-cancer effect of genistein and miR-27a-mediated MET signaling.

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“…Genetic rearrangements of the NTRK family have been reported in about 3% of NSCLC (62). Importantly, selective tyrosine kinase inhibitors against NTRK fusion proteins have demonstrated promising in vitro and in vivo anti-tumor activity in NSCLC (62)(63)(64).…”

Section: Ntrk Rearrangementsmentioning

confidence: 99%

Expanded molecular interrogation for potential actionable targets in non-squamous non-small cell lung cancer

et al. 2017

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The advent of targeted therapies has established new standards of care for defined molecular subsets of non-small cell lung cancer (NSCLC). Not only has this led to significant changes in the routine clinical management of lung cancer e.g., multiplexed genomic testing, but it has provided important principles and benchmarks for determining "actionability". At present, the clinical paradigms are most evolved for EGFR mutations and ALK rearrangements, where multiple randomized phase III trials have determined optimal treatment strategies in both treatment naïve and resistant settings. However, this may not always be feasible with low prevalence alterations e.g., ROS1 and BRAF mutations. Another emerging observation is that not all targets are equally "actionable", necessitating a rigorous preclinical, clinical and translational framework to prosecute new targets and drug candidates. In this review, we will cover the role of targeted therapies for NSCLC harbouring BRAF, MET, HER2 and RET alterations, all of which have shown promise in non-squamous non-small cell lung cancer (ns-NSCLC). We further review some early epigenetic targets in NSCLC, an area of emerging interest. With increased molecular segmentation of lung cancer, we discuss the upcoming challenges in drug development and implementation of precision oncology approaches, especially in light of the complex and rapidly evolving therapeutic landscape.

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Investigation of neurotrophic tyrosine kinase receptor 1 fusions and neurotrophic tyrosine kinase receptor family expression in non-small-cell lung cancer and sensitivity to AZD7451 in vitro

Cited by 28 publications

References 8 publications

Loss of YAP1 defines neuroendocrine differentiation of lung tumors

Loss of YAP1 defines neuroendocrine differentiation of lung tumors

Genistein inhibits A549 human lung cancer cell proliferation via miR-27a and MET signaling

Expanded molecular interrogation for potential actionable targets in non-squamous non-small cell lung cancer

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