NRG1 和 NRG2 融合阳性实体瘤恶性肿瘤：配体融合致癌作用的范例。
NRG1 and NRG2 fusion positive solid tumor malignancies: a paradigm of ligand-fusion oncogenesis.
机构信息
Chao Family Comprehensive Cancer Center, Orange, CA 92868, USA; University of California Irvine Susan and Henry Samueli College of Health Sciences, University of California Irvine School of Medicine, Department of Medicine, Division of Hematology-Oncology, Orange, CA 92868, USA; Division of Neurology, Department of Medicine, St. Marianna University School of Medicine, Kawasaki, Kanagawa, Japan.
Chao Family Comprehensive Cancer Center, Orange, CA 92868, USA; University of California Irvine Susan and Henry Samueli College of Health Sciences, University of California Irvine School of Medicine, Department of Medicine, Division of Hematology-Oncology, Orange, CA 92868, USA.
出版信息
Trends Cancer. 2022 Mar;8(3):242-258. doi: 10.1016/j.trecan.2021.11.003. Epub 2022 Jan 5.
Neuregulins (NRGs) are a family of six related physiological ligands all containing a receptor-binding epidermal growth factor (EGF)-like domain that mediate their binding to cellular receptors. Neuregulin-1 (NRG1) is the main physiological ligand to HER3. NRG1 fusion (NRG1+) was first reported in a breast cancer cell line and NRG2 fusions have recently been identified in solid tumors. It is postulated that NRG1 fusions, through mostly transmembrane fusion partners, result in NRG1 being concentrated in proximity to HER3, leading to its constitutive activation and oncogenesis. Recently, a monoclonal antibody that disrupts the binding of NRG1 to HER3 and HER3/HER2 heterodimerization has resulted in NRG1+ tumor shrinkage, suggesting that 'ligand-fusion' may be a novel mechanism of oncogenesis.
神经调节蛋白（NRGs）是一个包含六个相关生理配体的家族，它们都含有一个受体结合表皮生长因子（EGF）样结构域，介导它们与细胞受体的结合。神经调节蛋白-1（NRG1）是 HER3 的主要生理配体。NRG1 融合（NRG1+）首先在乳腺癌细胞系中报道，最近在实体瘤中发现了 NRG2 融合。据推测，NRG1 融合通过大多数跨膜融合伴侣，导致 NRG1 集中在接近 HER3 的位置，导致其组成性激活和致癌。最近，一种单克隆抗体可以破坏 NRG1 与 HER3 和 HER3/HER2 异二聚体的结合，导致 NRG1+肿瘤缩小，这表明“配体融合”可能是一种新的致癌机制。
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