TAM 受体在骨中的作用。

The Role of TAM Receptors in Bone.

机构信息

Department of Oncology, Hematology and Bone Marrow Transplantation with Section Pneumology, Hubertus Wald Comprehensive Cancer Center Hamburg, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany.

Department of Tumor Biology, Center of Experimental Medicine, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany.

出版信息

Int J Mol Sci. 2023 Dec 23;25(1):233. doi: 10.3390/ijms25010233.

DOI:10.3390/ijms25010233

PMID:38203403

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10779100/

Abstract

The TAM (TYRO3, MERTK, and AXL) family of receptor tyrosine kinases are pleiotropic regulators of adult tissue homeostasis maintaining organ integrity and self-renewal. Disruption of their homeostatic balance fosters pathological conditions like autoinflammatory or degenerative diseases including rheumatoid arthritis, lupus erythematodes, or liver fibrosis. Moreover, TAM receptors exhibit prominent cell-transforming properties, promoting tumor progression, metastasis, and therapy resistance in various cancer entities. Emerging evidence shows that TAM receptors are involved in bone homeostasis by regulating osteoblastic bone formation and osteoclastic bone resorption. Therefore, TAM receptors emerge as new key players of the regulatory cytokine network of osteoblasts and osteoclasts and represent accessible targets for pharmacologic therapy for a broad set of different bone diseases, including primary and metastatic bone tumors, rheumatoid arthritis, or osteoporosis.

摘要

TAM（TYRO3、MERTK 和 AXL）受体酪氨酸激酶家族是调节成人组织稳态的多效调节剂，维持器官完整性和自我更新。它们的内稳态平衡的破坏会促进自身炎症性或退行性疾病的发生，如类风湿关节炎、红斑狼疮或肝纤维化。此外，TAM 受体表现出明显的细胞转化特性，促进多种癌症实体的肿瘤进展、转移和治疗耐药性。新出现的证据表明，TAM 受体通过调节成骨细胞的骨形成和破骨细胞的骨吸收参与骨稳态。因此，TAM 受体成为成骨细胞和破骨细胞调节细胞因子网络的新的关键参与者，并代表了广泛的不同骨疾病（包括原发性和转移性骨肿瘤、类风湿关节炎或骨质疏松症）的药物治疗的可及靶点。