2017 Fiscal Year Final Research Report
Surfactant protein D inhibits activation of non-small cell lung cancer-associated mutant EGFR
Project/Area Number |
16K19461
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Research Category |
Grant-in-Aid for Young Scientists (B)
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Allocation Type | Multi-year Fund |
Research Field |
Respiratory organ internal medicine
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Research Institution | Sapporo Medical University |
Principal Investigator |
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Co-Investigator(Renkei-kenkyūsha) |
TAKAHASHI MOTOKO 札幌医科大学, 医学部, 教授 (00303941)
TAKAHASHI HIROKI 札幌医科大学, 医学部, 教授 (60231396)
SAKUMA YUJI 札幌医科大学, 医学部, 准教授 (10364514)
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Project Period (FY) |
2016-04-01 – 2018-03-31
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Keywords | 肺サーファクタント蛋白質D / 変異型EGFR / 肺がん / 糖鎖 / レクチン |
Outline of Final Research Achievements |
We have previously demonstrated that SP-D suppressed wild-type EGFR signaling by blocking ligand binding to EGFR. Analysis of patients with lung adenocarcinoma to examine associations between serum SP-D levels and clinical outcome indicated that in TKI-treated patients with lung cancer harboring EGFR mutations, high serum SP-D levels correlated with prolonged overall survival. We herein demonstrate that SP-D downregulates ligand-independent signaling in cells harboring EGFR mutations. SP-D inhibits ligand-independent dimerization of EGFR mutants and dimerization-independent activation of EGFR mutants. SP-D augmented the viability-suppressing effects of EGFR-TKIs. It is possible that the suppressive effects of SP-D on EGF signaling might be implicated in improved clinical outcomes in patients with EGFR mutant lung cancer and high serum SP-D levels.
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Free Research Field |
呼吸器内科
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