PO.TB10.03 · 肿瘤生物学
髓源性抑制细胞通过ARID1A/AKR1C2轴介导HR+/HER2-乳腺癌的铁死亡耐药
Myeloid-derived suppressor cells mediate ferroptosis resistance in HR+/HER2- breast cancer via the ARID1A/AKR1C2 axis
作者与单位 Authors & Affiliations
摘要 Abstract
中文摘要
乳腺癌是女性最常见的恶性肿瘤，约70%的病例被归类为HR+/HER2-亚型。复发和转移仍是乳腺癌患者死亡的主要原因。铁死亡耐药已被认为是乳腺癌进展的关键因素，但其与髓源性抑制细胞（MDSCs）——肿瘤微环境的关键组成部分——之间的关系在很大程度上仍未被探索。在本研究中，我们证明将HR+/HER2-乳腺癌细胞与MDSCs共孵育可显著降低其对铁死亡诱导剂的敏感性，且该过程与ARID1A表达的下调密切相关。进一步的生物信息学分析和功能性细胞实验表明，ARID1A缺失通过表观遗传调控驱动了铁死亡抑制基因AKR1C2的显著上调。总体而言，我们的发现揭示了MDSCs通过调控HR+/HER2-乳腺癌细胞中的ARID1A表达来调节AKR1C2转录，从而为开发针对乳腺癌的新型治疗靶点提供了有前景的策略。
查看英文原文 English abstract
Breast cancer is the most common malignancy in women, with approximately 70% of cases classified as the HR+/HER2- subtype. Recurrence and metastasis remain the leading causes of mortality in breast cancer patients. Resistance to ferroptosis has been recognized as a key factor in breast cancer progression, yet its relationship with myeloid-derived suppressor cells (MDSCs)-a critical component of the tumor microenvironment-has remained largely unexplored. In this study, we demonstrated that co-incubation of HR+/HER2- breast cancer cells with MDSCs significantly reduced their sensitivity to ferroptosis inducers and this process was closely associated with the downregulation of ARID1A expression. Further bioinformatic analysis and functional cellular experiments indicated that ARID1A loss drived the marked upregulation of the ferroptosis-suppressive gene AKR1C2 through epigenetic regulation. Overall, our findings reveal that MDSCs modulate AKR1C2 transcription by regulating ARID1A expression in HR+/HER2- breast cancer cells, thereby providing a promising strategy for the development of novel therapeutic targets against breast cancer.
利益披露 Disclosure
G. Chen, None..
J. Yu, None.