Department of Radiotherapy, Shaoxing People's Hospital, Shaoxing Hospital of Zhejiang University, Shaoxing, Zhejiang, China (mainland).
Clinical Laboratory Center, Shaoxing People's Hospital, Shaoxing Hospital of Zhejiang University, Shaoxing, Zhejiang, China (mainland).
Med Sci Monit. 2019 Apr 1;25:2352-2360. doi: 10.12659/MSM.915690.
BACKGROUND High-mobility group box 1 (HMGB1) is an essential contributor towards initiation and progression of many kinds of cancers. Nevertheless, our understanding of the molecular etiology of HMGB1-modulated vasculogenesis, as well as invasion, of breast cancer is poor. This study explored HMGB1 expression in breast cancer and its role in the development and spread of malignancy. MATERIAL AND METHODS We enrolled 15 patients with breast cancer who received primary surgery at the Department of Thyroid and Breast Surgery in our hospital. HMGB1 was recorded and analyzed. RESULTS Our investigation successfully proves that HMGB1 is upregulated in breast cancer tissues in comparison to the surrounding non-malignant tissues. HMGB1 enhanced vessel formation in breast cancer tissues by regulating hypoxia-inducible factor 1 (HIF-1alpha), which in turn upregulates the expression of VEGF. Furthermore, HMGB1-mediated upregulation of HIF-1alpha relies on its ability to stimulate the phosphatidylinositol 3-kinase (PI3K) pathway to reinforce AKT subunit phosphorylation. HMGB1 overexpression reinforces the vasculogenesis in malignancies not only in vivo but also in vitro. Additionally, shRNA knockdown of HMGB1 prohibited the vessel-forming and invasive capabilities, downregulated VEGF and HIF-1alpha, and suppressed AKT phosphorylation in breast cancer cells. Most importantly, PI3K/AKT axis suppression eliminated the effect of HMGB1-modulated vascularization and invasion in breast cancer cells. CONCLUSIONS Our research indicates that HMGB1 serves as a crucial regulator of malignant cell-modulated vessel formation and is involved in the development of malignancy. Our findings indicate that HMGB1 is a promising target for breast cancer treatment.
高迁移率族蛋白 B1（HMGB1）是多种癌症起始和进展的重要贡献者。然而，我们对 HMGB1 调节血管生成以及乳腺癌侵袭的分子病因学的理解还很有限。本研究探讨了 HMGB1 在乳腺癌中的表达及其在恶性肿瘤发展和扩散中的作用。
我们招募了在我院甲状腺乳腺外科接受初次手术的 15 例乳腺癌患者，记录并分析 HMGB1。
我们的研究成功地证明，HMGB1 在乳腺癌组织中上调，与周围非恶性组织相比。HMGB1 通过调节缺氧诱导因子 1（HIF-1alpha）增强乳腺癌组织中的血管形成，进而上调 VEGF 的表达。此外，HMGB1 介导的 HIF-1alpha 上调依赖于其刺激磷脂酰肌醇 3-激酶（PI3K）途径来增强 AKT 亚基磷酸化的能力。HMGB1 的过表达不仅在体内，而且在体外也增强了恶性肿瘤的血管生成。此外，HMGB1 的 shRNA 敲低抑制了乳腺癌细胞的血管生成和侵袭能力，下调了 VEGF 和 HIF-1alpha，并抑制了 AKT 磷酸化。最重要的是，PI3K/AKT 轴抑制消除了 HMGB1 调节的乳腺癌细胞血管生成和侵袭的作用。
我们的研究表明，HMGB1 是恶性细胞调节血管生成的关键调节剂，并参与了恶性肿瘤的发生。我们的研究结果表明，HMGB1 是治疗乳腺癌的一个有前途的靶点。
