Wu Lige, Xing Puyuan, Li Junling
Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Future Oncol. 2025 Jul;21(17):2251-2259. doi: 10.1080/14796694.2025.2514417. Epub 2025 Jun 3.
The DNAJ/HSP40 family consists of three distinct subfamilies (DNAJA, DNAJB, and DNAJC) and is the largest and most diverse co-chaperone proteins for HSP70. The DNAJA subfamily, comprising four members, assumes a pivotal role in various pathological conditions such as cystic fibrosis, neurodegenerative disorders, and cancer. This review comprehensively investigates the participation and underlying mechanisms of DNAJA proteins in tumor proliferation and metastasis, with a specific focus on their influence on the accumulation of mutant p53 proteins. Furthermore, we conducted an extensive examination of compounds utilizing computer-based techniques that specifically target DNAJA or its associated pathways, thereby offering novel insights for the development of cutting-edge combination therapies in the realm of cancer treatment. Our findings highlight the potential significance of targeting the DNAJA subfamily as a promising approach for anti-tumor therapy. Simultaneously, we also highlighted the limitations of current DNAJA research and proposed future directions for advancement in this field. We anticipate that DNAJA will emerge as a novel therapeutic target for anti-tumor interventions.
DNAJ/HSP40家族由三个不同的亚家族(DNAJA、DNAJB和DNAJC)组成,是HSP70最大且最多样化的共伴侣蛋白。DNAJA亚家族由四个成员组成,在诸如囊性纤维化、神经退行性疾病和癌症等各种病理状况中发挥关键作用。本综述全面研究了DNAJA蛋白在肿瘤增殖和转移中的参与情况及潜在机制,特别关注它们对突变型p53蛋白积累的影响。此外,我们利用基于计算机的技术对专门靶向DNAJA或其相关途径的化合物进行了广泛研究,从而为癌症治疗领域前沿联合疗法的开发提供了新见解。我们的研究结果突出了靶向DNAJA亚家族作为一种有前景的抗肿瘤治疗方法的潜在重要性。同时,我们也强调了当前DNAJA研究的局限性,并提出了该领域未来的发展方向。我们预计DNAJA将成为抗肿瘤干预的新型治疗靶点。