Insulin-like growth factor binding protein-3 (IGFBP-3) is a member of the IGFBP family that has high affinity for IGFs and functions as either an oncogene or tumor suppressor in various types of cancer. We previously found that IGFBP3 mRNA levels are higher in endophytic-type human tongue squamous cell carcinoma (TSCC) that is more invasive and more prone to metastasis than exophytic and superficial types. This finding prompted us to investigate the roles of IGFBP-3 in TSCC using SAS cells, which were originally derived from endophytic-type TSCC. Specifically, we used SAS cells that express a fluorescent ubiquitination-based cell-cycle indicator (Fucci). RNA-sequencing analysis indicated that IGFBP-3 is associated with cell migration and cell growth. In fact, IGFBP-3 knockdown downregulates cell migration and causes cells to arrest in G₁. This migratory potential appears to be cell cycle–independent. IGFBP-3 knockdown also reduced levels of secreted IGFBP-3; however, decreased migratory potential was not rescued by exogenous recombinant human IGFBP-3. Furthermore, ERK activity was downregulated by IGFBP-3 depletion, which suggests that MEK/ERK signaling may be involved in IGFBP-3-mediated cell migration. We therefore conclude that intracellular IGFBP-3 enhances cell migration independently of the cell cycle in TSCC with a higher metastatic potential.

胰岛素样生长因子结合蛋白 3 (IGFBP-3) 是 IGFBP 家族的成员，对 IGF 具有高亲和力，并在各种类型的癌症中充当癌基因或肿瘤抑制因子。我们之前发现IGFBP3内生型人舌鳞状细胞癌 (TSCC) 的 mRNA 水平较高，与外生型和浅表型相比，TSCC 更具侵袭性且更容易转移。这一发现促使我们使用最初来源于内生型 TSCC 的 SAS 细胞研究 IGFBP-3 在 TSCC 中的作用。具体来说，我们使用了表达基于荧光泛素化的细胞周期指示剂 (Fucci) 的 SAS 细胞。RNA测序分析表明IGFBP-3与细胞迁移和细胞生长有关。事实上，IGFBP-3 敲低下调细胞迁移并导致细胞在 G _1中停滞. 这种迁移潜力似乎与细胞周期无关。IGFBP-3 敲低也降低了分泌的 IGFBP-3 水平；然而，外源重组人 IGFBP-3 并没有挽救降低的迁移潜力。此外，ERK 活性被 IGFBP-3 耗竭下调，这表明 MEK/ERK 信号可能参与 IGFBP-3 介导的细胞迁移。因此，我们得出结论，细胞内 IGFBP-3 在具有更高转移潜力的 TSCC 中独立于细胞周期增强细胞迁移。