Department of Hematology, The First Affiliated Hospital of Xi'an Medical University, Xi'an, China.
Department of General Practice, The First Affiliated Hospital of Xi'an Medical University, Xi'an, China.
Environ Toxicol. 2022 Aug;37(8):1934-1943. doi: 10.1002/tox.23540. Epub 2022 Apr 20.
Sclerostin domain-containing 1 (SOSTDC1) has been documented as a key tumor-associated protein that is differentially expressed in multiple malignancies. However, the function of SOSTDC1 in acute myeloid leukemia (AML) is unexplored. The goal of this work was to assess the possible role of SOSTDC1 in AML. Our data showed decreased SOSTDC1 level in bone marrow from AML patients, and patients with low levels of SOSTDC1 had a reduced survival rate. SOSTC1 upregulation restrained the proliferative ability and promoted the apoptotic rate of AML cells. SOSTDC1 suppressed the activation of the Wnt/β-catenin pathway in AML cells. Reactivation of the Wnt/β-catenin pathway reversed SOSTDC1-mediated antitumor effects. SOSTDC1 upregulation weakened the tumorigenicity of AML cells in vivo. Collectively, our work demonstrates that SOSTDC1 has a tumor-inhibiting role in AML via downregulation of the Wnt/β-catenin pathway. This work underscores a key function for the SOSTDC1/Wnt/β-catenin pathway in AML.
骨硬化蛋白结构域包含蛋白 1（SOSTDC1）已被证实为一种关键的肿瘤相关蛋白，在多种恶性肿瘤中差异表达。然而，SOSTDC1 在急性髓系白血病（AML）中的功能尚不清楚。本研究旨在评估 SOSTDC1 在 AML 中的可能作用。我们的数据显示，AML 患者骨髓中 SOSTDC1 水平降低，SOSTDC1 水平低的患者生存率降低。SOSTC1 的上调抑制了 AML 细胞的增殖能力并促进了其凋亡率。SOSTDC1 抑制了 AML 细胞中 Wnt/β-catenin 通路的激活。Wnt/β-catenin 通路的再激活逆转了 SOSTDC1 介导的抗肿瘤作用。SOSTDC1 的上调减弱了 AML 细胞在体内的致瘤性。综上所述，我们的工作表明，SOSTDC1 通过下调 Wnt/β-catenin 通路在 AML 中发挥抑瘤作用。这项工作强调了 SOSTDC1/Wnt/β-catenin 通路在 AML 中的关键作用。
