LGR4 promotes proliferation and homing via activation of the NF‑&kappa;B signaling pathway in multiple myeloma

He,Nihan; Yang,Qin; Li,Zhengjiang; Guo,Jiaojiao; Kuang,Chunmei; Zhu,Yinghong; Liu,Xing; Chen,Xun; Shi,Fangming; Feng,Xiangling; An,Gang; Zhang,Guoping; Zhou,Wen

doi:10.3892/ijo.2025.5718

LGR4 promotes proliferation and homing via activation of the NF‑κB signaling pathway in multiple myeloma

Authors:
- Nihan He
- Qin Yang
- Zhengjiang Li
- Jiaojiao Guo
- Chunmei Kuang
- Yinghong Zhu
- Xing Liu
- Xun Chen
- Fangming Shi
- Xiangling Feng
- Gang An
- Guoping Zhang
- Wen Zhou
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Affiliations: National Clinical Research Center for Geriatric Disorders, Key Laboratory for Carcinogenesis and Invasion, Chinese Ministry of Education, Furong Laboratory, Changsha, Hunan 410008, P.R. China, Department of Hematology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China, Xiangya School of Public Health, Central South University, Changsha, Hunan 410006, P.R. China, State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Tianjin 300074, P.R. China
Published online on: January 3, 2025 https://doi.org/10.3892/ijo.2025.5718
Article Number: 12
Copyright: © He et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Multiple myeloma (MM) is a plasma cell malignancy characterized by clonal proliferation in the bone marrow (BM). Previously, it was reported that G‑protein‑coupled receptor 4 (LGR4) contributed to early hematopoiesis and was associated with poor prognosis in patients with MM. However, the mechanism of cell homing and migration, which is critical for MM progression, remains unclear. In the present study, cell counting, cell cycle and BrdU assays were performed to evaluate cell proliferation. Transwell assay and Xenograft mouse models were performed to evaluate cell migration and homing ability both in vitro and in vivo. I was found that overexpression of LGR4 promotes MM cell adhesion, migration and homing to BM both in vitro, while exacerbating osteolytic bone destruction in vivo. However, the LGR4 knockdown displayed the opposite effect. Further mechanistic studies demonstrated that LGR4 activated the nuclear factor kappa B (NF‑κB) signaling pathway and migration‑related adhesion molecule, thus promoting MM cell homing. Moreover, inhibiting the NF‑κB pathway was found to suppress MM cell homing. These findings identify LGR4 as a critical regulator of myeloma cell migration, homing and tumorigenesis, offering a potential therapeutic strategy for MM treatment.

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