2013 Fiscal Year Final Research Report
Elucidation of trans-activation mechanism from TRAIL receptor to EGFR
| Project/Area Number |
23590308
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
General pharmacology
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| Research Institution | Showa University |
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Principal Investigator |
OHMORI Tohru 昭和大学, 腫瘍分子生物学研究所, 准教授 (10276529)
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| Co-Investigator(Kenkyū-buntansha) |
YAMAOKA Toshimitsu 昭和大学, 腫瘍分子生物学研究所, 講師 (40384359)
HIROSE Takashi 昭和大学, 内科学講座呼吸器内科学分野, 准教 (40307038)
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| Project Period (FY) |
2011 – 2013
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| Keywords | EGFR / TRAIL / EGFR-TKI / 薬剤耐性 / crosstalk signal |
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| Research Abstract |
We established EGFR-TKI-resistant non-small cell lung cancer (NSCLC) cell lines and found that these cell lines acquired collateral sensitivity to Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) (about 70 times) as compared with parental cell line. In parental PC-9, anti-tumor effect of TRAIL was restricted, because TRAIL activates not only apoptotic signaling but also anti-apoptotic signaling through Akt/NFkB activation by cross talk signaling from TRAIL receptor to EGFR. In case of the resistant cell lines that overexpressed c-MET, the crosstalk signaling from TRAIL receptor to c-MET was not observed, and TRAIL-mediated Akt/NFkB activation was quite diminished. From these observations, EGFR-TKI/TRAIL combination is thought to be useful therapy for NSCLC.
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