Deng JiaLi, Zhou Jie, Jiang BinYuan
Medical Research Center, The Affiliated Changsha Central Hospital, Hengyang Medical School, University of South China, Changsha, 410004, China.
Department of Clinical Laboratory, The Affiliated Changsha Central Hospital, Hengyang Medical School, University of South China, Changsha, 410004, China.
Discov Oncol. 2024 Oct 15;15(1):559. doi: 10.1007/s12672-024-01414-1.
Protein shuttling between the cytoplasm and nucleus is a unique phenomenon in eukaryotic organisms, integral to various cellular functions. Membrane-bound transcription factors (MTFs), a specialized class of nucleocytoplasmic shuttling proteins, are anchored to the cell membrane and enter the nucleus upon ligand binding to exert their transcriptional regulatory functions. MTFs are crucial in cellular signal transduction, and aberrant nucleocytoplasmic shuttling of MTFs is closely associated with tumor initiation, progression, and resistance to anticancer therapies. Studies have demonstrated that MTFs, such as human epidermal growth factor receptor (HER), fibroblast growth factor receptor (FGFR), β-catenin, Notch, insulin-like growth factor 1 receptor (IGF-1R), and insulin receptor (IR), play critical roles in tumorigenesis and cancer progression. Targeted therapies developed against HERs and FGFRs, among these MTFs, have yielded significant success in cancer treatment. However, the development of drug resistance remains a major challenge. As research on MTFs progress, it is anticipated that additional MTF-targeted therapies will be developed to enhance cancer treatment. In this review, we summarized recent advancements in the study of MTFs and their roles in carcinogenesis and therapy, aiming to provide valuable insights into the potential of targeting MTF pathways for the reseach of therapeutic strategies.
蛋白质在细胞质和细胞核之间穿梭是真核生物中的一种独特现象，对各种细胞功能至关重要。膜结合转录因子（MTF）是一类特殊的核质穿梭蛋白，锚定在细胞膜上，在配体结合后进入细胞核以发挥其转录调节功能。MTF在细胞信号转导中至关重要，MTF异常的核质穿梭与肿瘤的发生、发展以及对抗癌治疗的耐药性密切相关。研究表明，MTF，如人类表皮生长因子受体（HER）、成纤维细胞生长因子受体（FGFR）、β-连环蛋白、Notch、胰岛素样生长因子1受体（IGF-1R）和胰岛素受体（IR），在肿瘤发生和癌症进展中起关键作用。针对这些MTF中的HER和FGFR开发的靶向治疗在癌症治疗中取得了显著成功。然而，耐药性的产生仍然是一个重大挑战。随着对MTF研究的进展，预计将开发更多针对MTF的治疗方法以加强癌症治疗。在这篇综述中，我们总结了MTF研究的最新进展及其在致癌作用和治疗中的作用，旨在为靶向MTF途径以研究治疗策略的潜力提供有价值的见解。
