Department of Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
Pittsburgh VA Health System, Pittsburgh, Pennsylvania, United States of America.
PLoS One. 2023 Mar 29;18(3):e0283749. doi: 10.1371/journal.pone.0283749. eCollection 2023.
Axl, a member of the TAM receptor family has been broadly suggested to play a key role in tumor metastasis. However, the function of Axl in the invasion and metastasis of melanoma, the most lethal skin cancer, remains largely unknown. In the present study, we found that melanoma cell lines present variable protein levels of Axl and Tyro3; interestingly, MerTK is not noted at detectable levels in any of tested MGP (metastatic growth phase) cell lines. Treatment with recombinant human Gas6 significantly activates Akt in the Axl-expressing WM852 and IgR3 lines but just slightly in WM1158. IgR3, WM852 and WM1158 demonstrate different autocrine signaling. Knockdown of Axl by siRNA or the treatment with Axl-specific inhibitor R428 dramatically inhibits the migration and invasion of both IgR3 and WM852 in vitro. These findings suggest that Axl enhances the invasion of melanoma cells.
Axl 是 TAM 受体家族的成员，广泛认为在肿瘤转移中发挥关键作用。然而，Axl 在黑色素瘤（最致命的皮肤癌）侵袭和转移中的功能在很大程度上尚不清楚。在本研究中，我们发现黑色素瘤细胞系存在 Axl 和 Tyro3 的可变蛋白水平；有趣的是，在任何测试的 MGP（转移生长阶段）细胞系中均未检测到 MerTK。用重组人 Gas6 处理可显著激活 Axl 表达的 WM852 和 IgR3 系中的 Akt，但在 WM1158 中仅稍有激活。IgR3、WM852 和 WM1158 表现出不同的自分泌信号。用 siRNA 敲低 Axl 或用 Axl 特异性抑制剂 R428 处理可显著抑制 IgR3 和 WM852 在体外的迁移和侵袭。这些发现表明 Axl 增强了黑色素瘤细胞的侵袭。
