Department of Medical Science, College of Medicine, Chungnam National University, Daejeon 35015, Republic of Korea.
Department of Pathology, College of Medicine, Chungnam National University, Daejeon 35015, Republic of Korea.
Int J Mol Sci. 2023 Feb 2;24(3):2925. doi: 10.3390/ijms24032925.
Growth differentiation factor 15 (GDF15) has been reported to play an important role in cancer and is secreted and involved in the progression of various cancers, including ovarian cancer, prostate cancer, and thyroid cancer. Nevertheless, the functional mechanism of GDF15 in gastric cancer is still unclear. Immunohistochemical staining was performed to estimate the expression of GDF15 in 178 gastric cancer tissues. The biological role and action mechanism of GDF15 were investigated by examining the effect of GDF15 knockdown in AGS and SNU216 gastric cancer cells. Here, we report that the high expression of GDF15 was associated with invasion depth ( = 0.002), nodal involvement ( = 0.003), stage III/IV ( = 0.01), lymphatic invasion ( = 0.05), and tumor size ( = 0.049), which are related to poor survival in gastric cancer patients. GDF15 knockdown induced G0/G1 cell cycle arrest and remarkably inhibited cell proliferation and reduced cell motility, migration, and invasion compared to the control. GDF15 knockdown inhibited the epithelial-mesenchymal transition by regulating the STAT3 phosphorylation signaling pathways. Taken together, our results indicate that GDF15 expression is associated with aggressive gastric cancer by promoting STAT3 phosphorylation, suggesting that the GDF15-STAT3 signaling axis is a potential therapeutic target against gastric cancer progression.
生长分化因子 15（GDF15）已被报道在癌症中发挥重要作用，并分泌参与各种癌症的进展，包括卵巢癌、前列腺癌和甲状腺癌。然而，GDF15 在胃癌中的功能机制尚不清楚。通过免疫组织化学染色来评估 178 例胃癌组织中 GDF15 的表达。通过检查 GDF15 在 AGS 和 SNU216 胃癌细胞中的敲低作用，研究了 GDF15 的生物学作用和作用机制。在这里，我们报告 GDF15 的高表达与浸润深度（=0.002）、淋巴结受累（=0.003）、III/IV 期（=0.01）、淋巴浸润（=0.05）和肿瘤大小（=0.049）有关，这些因素与胃癌患者的不良预后有关。与对照组相比，GDF15 敲低诱导 G0/G1 细胞周期停滞，显著抑制细胞增殖，并降低细胞迁移、侵袭能力。GDF15 敲低通过调节 STAT3 磷酸化信号通路抑制上皮-间充质转化。总之，我们的研究结果表明，GDF15 表达通过促进 STAT3 磷酸化与侵袭性胃癌相关，提示 GDF15-STAT3 信号轴可能是治疗胃癌进展的潜在靶点。
