State Key Laboratory of Ophthalmology, Optometry and Vision Science, Wenzhou Medical University, Wenzhou, China.
The Eye Hospital, School of Ophthalmology & Optometry, Wenzhou Medical University, Wenzhou, China.
Cell Death Dis. 2023 Jan 23;14(1):55. doi: 10.1038/s41419-023-05590-w.
Autophagy dysfunction is one of the common causes of tumor formation and plays an important role in uveal melanoma (UM). However, little is known about the regulatory mechanisms of autophagy in UM. Here, we show that PTK6 can promote the proliferation, migration, and invasion of UM cells by inhibiting autophagy. SOCS3 can inhibit the proliferation, migration, and invasion of UM cells. Overexpression of SOCS3 can partially rescue the PTK6-induced promotion of UM cell proliferation, migration, and invasion. Mechanistically, PTK6 can bind to SOCS3, and SOCS3 can downregulate the expression of PTK6. Furthermore, PTK6 can upregulate the phosphorylation of mTOR to inhibit autophagy. Taken together, our findings demonstrate the functions of PTK6 and SOCS3 in UM cells and targeting the SOCS3-PTK6 signaling axis might be a novel and promising therapeutic strategy for patients with UM.
自噬功能障碍是肿瘤形成的常见原因之一，在葡萄膜黑色素瘤（UM）中起重要作用。然而，自噬在 UM 中的调控机制知之甚少。在这里，我们发现 PTK6 可以通过抑制自噬来促进 UM 细胞的增殖、迁移和侵袭。SOCS3 可以抑制 UM 细胞的增殖、迁移和侵袭。SOCS3 的过表达可以部分挽救 PTK6 诱导的 UM 细胞增殖、迁移和侵袭的促进作用。机制上，PTK6 可以与 SOCS3 结合，SOCS3 可以下调 PTK6 的表达。此外，PTK6 可以上调 mTOR 的磷酸化以抑制自噬。总之，我们的研究结果表明了 PTK6 和 SOCS3 在 UM 细胞中的作用，靶向 SOCS3-PTK6 信号轴可能是治疗 UM 患者的一种新的有前途的治疗策略。
