Department of Breast and Thyroid Surgery, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200072, China.
Department of Breast Surgery, Guizhou Provincial People's Hospital, Guiyang, 550002, China.
Cell Death Dis. 2023 Feb 11;14(2):106. doi: 10.1038/s41419-023-05657-8.
Breast cancer (BC) is the most common malignant tumor in women worldwide, and its recurrence and metastasis negatively affect patient prognosis. However, the mechanisms underlying its tumorigenesis and progression remain unclear. Recently, the influence of dermatopontin (DPT), which is an extracellular matrix protein, has been proposed in the development of cancer. Here we found that DNMT3a-mediated DPT, promoter hypermethylation results in the downregulation of DPT expression in breast cancer and its low expression correlated with poor prognosis. Notably, DPT directly interacted with YAP to promote YAP Ser127 phosphorylation, and restricted the translocation of endogenous YAP from the cytoplasm to the nucleus, thereby suppressing malignant phenotypes in BC cells. In addition, Ectopic YAP overexpression reversed the inhibitory effects of DPT on BC growth and metastasis. Our study showed the critical role of DPT in regulating BC progression, making it easier to explore the clinical potential of modulating DPT/YAP activity in BC targeted therapies.
乳腺癌（BC）是全球女性最常见的恶性肿瘤，其复发和转移对患者的预后产生负面影响。然而，其肿瘤发生和发展的机制仍不清楚。最近，细胞外基质蛋白——真皮桥蛋白（DPT）在癌症发展中的影响被提出。在这里，我们发现 DNMT3a 介导的 DPT 启动子超甲基化导致乳腺癌中 DPT 的表达下调，其低表达与不良预后相关。值得注意的是，DPT 直接与 YAP 相互作用，促进 YAP Ser127 磷酸化，并限制内源性 YAP 从细胞质向细胞核的易位，从而抑制 BC 细胞的恶性表型。此外，异位 YAP 过表达逆转了 DPT 对 BC 生长和转移的抑制作用。我们的研究表明 DPT 在调节 BC 进展中的关键作用，这使得探索在 BC 靶向治疗中调节 DPT/YAP 活性的临床潜力变得更加容易。
