論文 - 詳細
| RRC ID | 70512 |
|---|---|
| 著者 | Jimbo K, Nakajima-Takagi Y, Ito T, Koide S, Nannya Y, Iwama A, Tojo A, Konuma T. |
| タイトル | Immunoglobulin superfamily member 8 maintains myeloid leukemia stem cells through inhibition of β-catenin degradation. |
| ジャーナル | Leukemia |
| Abstract |
The identification of characteristic differences between cancer stem cells and their normal counterparts remains a key challenge for cancer treatment. Here, we investigated the role of immunoglobulin superfamily member 8 (Igsf8, also known as EWI-2, PGRL, and CD316) on normal and malignant hematopoietic stem cells, mainly using the conditional knockout model. Deletion of Igsf8 did not affect steady state hematopoiesis, but it led to a significant improvement of survival in mouse myeloid leukemia models. Deletion of Igsf8 significantly depletes leukemia stem cells (LSCs) through enhanced apoptosis and β-catenin degradation. At a molecular level, we found that activation of β-catenin in LSCs depends on Igsf8, which promotes the association of FZD4 with its co-receptor LRP6 in the presence of Igsf8. Similarly, IGSF8 inhibition blocks the colony-forming ability of LSCs and improves the survival of recipients in xenograft models of myeloid leukemia. Collectively, these data indicate strong genetic evidence identifying Igsf8 as a key regulator of myeloid leukemia and the possibility that targeting IGSF8 may serve as a new therapeutic approach against myeloid leukemia. |
| 巻・号 | 36(6) |
| ページ | 1550-1562 |
| 公開日 | 2022-6-1 |
| DOI | 10.1038/s41375-022-01564-7 |
| PII | 10.1038/s41375-022-01564-7 |
| PMID | 35418614 |
| MeSH | Animals Carrier Proteins / metabolism* Frizzled Receptors / metabolism Hematopoietic Stem Cells / metabolism Humans Immunoglobulins Leukemia, Myeloid, Acute* / metabolism Membrane Proteins / metabolism* Mice Neoplastic Stem Cells / pathology Transcription Factors / metabolism beta Catenin / genetics beta Catenin / metabolism* |
| IF | 8.665 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 3 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 実験動物マウス | RBRC05637 |