UBE2L6 promotes invasion and metastasis of triple-negative breast cancer by enhancing autophagy through STK38 ISGylation.

Although aberrant activation of autophagy is well known in triple-negative breast cancer (TNBC), its functional roles and underlying mechanisms remain largely unknown. In the present study, we found that high UBE2L6 expression was strongly associated with aggressive clinical features in TNBC. We demonstrated that UBE2L6 promoted migration, invasion, and lung metastasis of TNBC by enhancing STK38-mediated autophagy. Mechanistically, UBE2L6 stabilized STK38 by promoting its ISGylation and inhibiting its ubiquitin-proteasomal degradation. Therefore, targeting UBE2L6 and modulating the STK38 ISGylation-autophagy axis represent potential intervention points in TNBC.