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Myeloma–Bone Interaction : A Vicious Cycle via TAK1–PIM2 Signaling
https://tokushima-u.repo.nii.ac.jp/records/2010241
https://tokushima-u.repo.nii.ac.jp/records/201024198fa3c72-f449-4316-a76b-fca552284d61
| 名前 / ファイル | ライセンス | アクション |
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cancers_13_17_4441.pdf (520 KB)
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| Item type | 文献 / Documents(1) | |||||||||||||||||||||||
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| 公開日 | 2022-09-08 | |||||||||||||||||||||||
| アクセス権 | ||||||||||||||||||||||||
| アクセス権 | open access | |||||||||||||||||||||||
| 資源タイプ | ||||||||||||||||||||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_6501 | |||||||||||||||||||||||
| 資源タイプ | journal article | |||||||||||||||||||||||
| 出版社版DOI | ||||||||||||||||||||||||
| 関連識別子 | https://doi.org/10.3390/cancers13174441 | |||||||||||||||||||||||
| 関連名称 | 10.3390/cancers13174441 | |||||||||||||||||||||||
| 出版タイプ | ||||||||||||||||||||||||
| 出版タイプ | VoR | |||||||||||||||||||||||
| 出版タイプResource | http://purl.org/coar/version/c_970fb48d4fbd8a85 | |||||||||||||||||||||||
| タイトル | ||||||||||||||||||||||||
| タイトル | Myeloma–Bone Interaction : A Vicious Cycle via TAK1–PIM2 Signaling | |||||||||||||||||||||||
| 著者 |
原田, 武志
× 原田, 武志× 日浅, 雅博
WEKO
326
× 寺町, 順平
WEKO
384
× 安倍, 正博
WEKO
1634
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| 抄録 | ||||||||||||||||||||||||
| 内容記述 | Myeloma cells interact with their ambient cells in the bone, such as bone marrow stromal cells, osteoclasts, and osteocytes, resulting in enhancement of osteoclastogenesis and inhibition of osteoblastogenesis while enhancing their growth and drug resistance. The activation of the TAK1–PIM2 signaling axis appears to be vital for this mutual interaction, posing it as an important therapeutic target to suppress tumor expansion and ameliorate bone destruction in multiple myeloma. | |||||||||||||||||||||||
| 抄録 | ||||||||||||||||||||||||
| 内容記述 | Multiple myeloma (MM) has a propensity to develop preferentially in bone and form bone-destructive lesions. MM cells enhance osteoclastogenesis and bone resorption through activation of the RANKL–NF-κB signaling pathway while suppressing bone formation by inhibiting osteoblastogenesis from bone marrow stromal cells (BMSCs) by factors elaborated in the bone marrow and bone in MM, including the soluble Wnt inhibitors DKK-1 and sclerostin, activin A, and TGF-β, resulting in systemic bone destruction with loss of bone. Osteocytes have been drawn attention as multifunctional regulators in bone metabolism. MM cells induce apoptosis in osteocytes to trigger the production of factors, including RANKL, sclerostin, and DKK-1, to further exacerbate bone destruction. Bone lesions developed in MM, in turn, provide microenvironments suited for MM cell growth/survival, including niches to foster MM cells and their precursors. Thus, MM cells alter the microenvironments through bone destruction in the bone where they reside, which in turn potentiates tumor growth and survival, thereby generating a vicious loop between tumor progression and bone destruction. The serine/threonine kinases PIM2 and TAK1, an upstream mediator of PIM2, are overexpressed in bone marrow stromal cells and osteoclasts as well in MM cells in bone lesions. Upregulation of the TAK1–PIM2 pathway plays a critical role in tumor expansion and bone destruction, posing the TAK1–PIM2 pathway as a pivotal therapeutic target in MM. | |||||||||||||||||||||||
| キーワード | ||||||||||||||||||||||||
| 主題 | multiple myeloma | |||||||||||||||||||||||
| キーワード | ||||||||||||||||||||||||
| 主題 | bone microenvironment | |||||||||||||||||||||||
| キーワード | ||||||||||||||||||||||||
| 主題 | bone remodeling | |||||||||||||||||||||||
| キーワード | ||||||||||||||||||||||||
| 主題 | TAK1 | |||||||||||||||||||||||
| キーワード | ||||||||||||||||||||||||
| 主題 | PIM2 | |||||||||||||||||||||||
| 書誌情報 |
en : Cancers 巻 13, 号 17, p. 4441, 発行日 2021-09-03 |
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| 収録物識別子タイプ | ISSN | |||||||||||||||||||||||
| 収録物識別子 | 20726694 | |||||||||||||||||||||||
| 出版者 | ||||||||||||||||||||||||
| 出版者 | MDPI | |||||||||||||||||||||||
| 権利情報 | ||||||||||||||||||||||||
| 権利情報 | This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). | |||||||||||||||||||||||
| EID | ||||||||||||||||||||||||
| 識別子 | 387163 | |||||||||||||||||||||||
| 言語 | ||||||||||||||||||||||||
| 言語 | eng | |||||||||||||||||||||||
