Department of Hematology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, P.R. China.
Oncol Rep. 2017 Aug;38(2):967-974. doi: 10.3892/or.2017.5744. Epub 2017 Jun 22.
Klotho is a transmembrane protein and acts as an upstream modulator of insulin-like growth factor-1 receptor (IGF-1R) signaling, which was indicated to be involved in the pathogenesis of solid cancer and hematological malignancies, including T‑cell lymphoma. Although Klotho was recently identified as a tumor suppressor in several types of human malignancies, the potential role of Klotho in T‑cell lymphoma has not been reported. In the present study, we investigated the expression level and the molecular events of Klotho in T‑cell lymphoma. Significantly lower expression of Klotho was observed in T‑cell lymphoma patient samples compared to normal lymph nodes. Functional analysis after Klotho overexpression revealed significantly inhibited tumor cell viability in T‑cell lymphoma. Moreover, apoptosis of T‑cell lymphoma cells were induced after transfected with Klotho-overexpressing vectors. Forced expression of Klotho resulted in decline of activation of IGF-1R signaling, accompanied by decreased phosphorylation of its downstream targets, including AKT and ERK1/2. These data indicated that Klotho acts as a tumor suppressor via inhibiting IGF-1R signaling, thus suppressing the viability and promoting apoptosis in T‑cell lymphoma. Taken together, Klotho may serve as a potential target for the therapeutic intervention of T‑cell lymphoma.
Klotho 是一种跨膜蛋白，作为胰岛素样生长因子-1 受体 (IGF-1R) 信号的上游调节剂，其被表明参与实体癌和血液恶性肿瘤的发病机制，包括 T 细胞淋巴瘤。尽管 Klotho 最近被确定为几种类型人类恶性肿瘤中的肿瘤抑制因子，但 Klotho 在 T 细胞淋巴瘤中的潜在作用尚未报道。在本研究中，我们研究了 Klotho 在 T 细胞淋巴瘤中的表达水平和分子事件。与正常淋巴结相比，T 细胞淋巴瘤患者样本中 Klotho 的表达明显降低。Klotho 过表达后的功能分析显示，T 细胞淋巴瘤中的肿瘤细胞活力明显受到抑制。此外，转染 Klotho 过表达载体后诱导 T 细胞淋巴瘤细胞凋亡。Klotho 的强制表达导致 IGF-1R 信号的激活下降，其下游靶标包括 AKT 和 ERK1/2 的磷酸化减少。这些数据表明，Klotho 通过抑制 IGF-1R 信号作为肿瘤抑制因子发挥作用，从而抑制 T 细胞淋巴瘤的活力并促进其凋亡。总之，Klotho 可能成为 T 细胞淋巴瘤治疗干预的潜在靶点。
