Targeting HMGA1 contributes to immunotherapy in aggressive breast cancer while suppressing EMT,BIOCHEMICAL PHARMACOLOGY

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Targeting HMGA1 contributes to immunotherapy in aggressive breast cancer while suppressing EMT
BIOCHEMICAL PHARMACOLOGY ( IF 5.3 ) Pub Date : 2023-05-04 , DOI: 10.1016/j.bcp.2023.115582
Xing Chang ₁ , Jingang Liu ₁ , Qian Yang ₁ , Yu Gao ₂ , Xiaofei Ding ₃ , Junjun Zhao ₂ , Yang Li ₁ , Zi Liu ₁ , Zengqiang Li ₁ , Yingliang Wu ₁ , Daiying Zuo ₁

Affiliation

Metastasis is an obstacle to the clinical treatment of aggressive breast cancer (BC). Studies have shown that high mobility group A1 (HMGA1) is abnormally expressed in various cancers and mediates tumor proliferation and metastasis. Here, we provided more evidence that HMGA1 mediated epithelial to mesenchymal transition (EMT) through the Wnt/β-catenin pathway in aggressive BC. More importantly, HMGA1 knockdown enhanced antitumor immunity and improved the response to immune checkpoint blockade (ICB) therapy by upregulating programmed cell death ligand 1 (PD-L1) expression. Simultaneously, we revealed a novel mechanism by which HMGA1 and PD-L1 were regulated by the PD-L1/HMGA1/Wnt/β-catenin negative feedback loop in aggressive BC. Taken together, we believe that HMGA1 can serve as a target for the dual role of anti-metastasis and enhancing immunotherapeutic responses.

中文翻译：

靶向 HMGA1 有助于侵袭性乳腺癌的免疫治疗，同时抑制 EMT

转移是侵袭性乳腺癌（BC）临床治疗的障碍。研究表明，高迁移率 A1 组（HMGA1）在各种癌症中异常表达，并介导肿瘤增殖和转移。在这里，我们提供了更多证据表明，HMGA1 在侵袭性 BC 中通过 Wnt/β-catenin 通路介导上皮到间充质转化（EMT）。更重要的是，HMGA1 敲低通过上调程序性细胞死亡配体 1 （PD-L1）表达增强了抗肿瘤免疫力，并改善了对免疫检查点阻断（ICB）治疗的反应。同时，我们揭示了一种新的机制，即 HMGA1 和 PD-L1 在侵袭性 BC 中受 PD-L1/HMGA1/Wnt/β-catenin 负反馈回路的调节。综上所述，我们相信 HMGA1 可以作为抗转移和增强免疫治疗反应双重作用的靶点。

更新日期：2023-05-04

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