2022 Fiscal Year Final Research Report
Significance of LGR6 expression induced by Wnt pathway activation in lung cancer
Project/Area Number |
20K08533
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 53030:Respiratory medicine-related
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Research Institution | Gunma University |
Principal Investigator |
Sunaga Noriaki 群馬大学, 医学部附属病院, 講師 (70400778)
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Project Period (FY) |
2020-04-01 – 2023-03-31
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Keywords | 肺癌 |
Outline of Final Research Achievements |
We identified LGR6-related pathways and genes by mRNA sequencing analysis comparing the transcripts of CTNNB1-mutated non-small cell lung cancer (NSCLC) HCC15 and A427 cells with or without LGR6 knockdown. These genes include those that confer tumor progression and cancer cell stemness. In A427 cells, which exhibit biphasic growth pattern with sphere-forming and adherent cell components, LGR6 was highly expressed in the spheroids. mRNA sequencing analysis comparing the expression profiles of sphere-forming and adherent A427 cells uncovered several genes that have been associated with cancer cell stemness. Pathway analysis revealed that the common canonical pathway regulated by LGR6 in CTNNB1-mutated NSCLC cells and in sphere-forming A427 cells was "Pulmonary Fibrosis Idiopathic Signaling Pathway". These results highlight the therapeutic and prognostic significance of LGR6, potentially leading to the development of novel treatment strategies and biomarkers for lung cancer.
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Free Research Field |
医歯薬学
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Academic Significance and Societal Importance of the Research Achievements |
肺癌ではEGFR遺伝子変異をはじめとする様々なドライバー遺伝子変異の発見や分子標的治療薬が開発されている。一方で、Wnt経路活性化を呈する肺癌に対する治療法やバイオマーカーの開発はすすんでいない。本研究において、Wnt経路活性化により誘導されるLGR6発現が肺癌の増殖能を亢進し、LGR6高発現が肺癌の予後不良マーカーであることを見出した上で、LGR6が様々な遺伝子発現や「特発性肺線維症シグナル伝達経路」をはじめとする経路を制御することで腫瘍の促進や癌幹細胞化に関与している可能性が示唆された。本研究成果が肺癌の新規治療法や予後予測バイオマーカーの開発への礎になると考えられる。
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