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Toshio Kato

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    P1.03 - Biology (Not CME Accredited Session) (ID 935)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
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    • Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
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      P1.03-13 - eIF2β, A Subunit of Translation-Initiation Factor EIF2, as a Potential Therapeutic Target for Non-Small Cell Lung Cancer (ID 11293)

      16:45 - 18:00  |  Author(s): Toshio Kato

      • Abstract
      • Slides


      To identify potential therapeutic targets for non-small cell lung cancer (NSCLC), we recently performed a semi-genome wide shRNA screen in a NSCLC cell line H460 . Through this approach, we identified multiple potential targets for NSCLC (Kakumu et al. Cancer Sci, 2017). In the present study, to search for genes with more generalized potential as therapeutic targets, we did shRNA screen using the alternative NSCLC cell line H358 and combined its results with those of our previous screen.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      19 NSCLC cell lines, two cdk4/hTERT-immortalized normal human bronchial epithelial (HBEC) cell lines and primary NHBE culture were used. A semi-genome wide shRNA screen was performed with the DECIPHER library in H358, and its results were integrated with those of our previous screen in H460. Gene silencing was done with RNA interference followed by growth and cell cycle analyses.

      4c3880bb027f159e801041b1021e88e8 Result

      24 genes overlapped between results of two shRNA screens in H460 and H358 and we identified these as more generalized targets. Gene-annotation enrichment analysis showed that the RNA transport pathway including three genes is one of the overrepresented pathways in the 24 genes. Among the three genes, we determined to focus on eIF2β, a subunit of translation-initiation factor EIF2 because other two genes included in the RNA transport pathway, XPO1 and RAN are well characterized therapeutic targets for human cancers including lung cancer. eIF2β protein was more abundantly expressed in all the 19 lung cancer cell lines analyzed than in NHBE used as a control. To determine the clinical relevance of eIF2β in lung cancer, we examined eIF2β mRNA expression in lung adenocarcinoma tissues using TCGA dataset. These analyses showed significantly higher expression of eIF2β mRNA in lung adenocarcinoma tissues than in normal adjacent tissues. Importantly, we found that expression of eIF2β mRNA correlated with worse prognosis in patients with lung adenocarcinoma in multiple independent datasets, suggesting its potential as a prognostic marker. Next, we examined the effects of eIF2β knockdown on the growth of the H460 and H1975. Colorimetric growth and colony formation assays showed that eIF2β knockdown in H460 and H1975 suppresses cell growth and colony formation.

      8eea62084ca7e541d918e823422bd82e Conclusion

      eIF2β is highly expressed in NSCLC cells, and its expression correlates with poor prognosis in patients with lung adenocarcinoma. Knockdown of eIF2β caused G1 arrest in lung cancer cell lines. These results suggest that eIF2β is a potential therapeutic target for NSCLC and that it is a prognostic marker for lung adenocarcinoma.


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