PTK6 inhibits autophagy to promote uveal melanoma tumorigenesis by binding to SOCS3 and regulating mTOR phosphorylation

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.

Automated summary

Autophagy dysfunction is a common cause of tumor formation and plays a crucial role in uveal melanoma (UM). This study reveals that PTK6 inhibits autophagy to promote the proliferation, migration, and invasion of UM cells. In contrast, SOCS3 inhibits the proliferation, migration, and invasion of UM cells. Overexpression of SOCS3 partially reverses the PTK6-induced promotion of UM cell proliferation, migration, and invasion.