ABSTRACT
Although Janus kinase 2 (JAK2) plays a critical role in the progression of triple-negative breast cancer (TNBC), its inhibitors are incapable of eradicating these tumor cells, implicating drug resistance mechanisms exist. Our evidences show that TNBC cells express high level of Serine/Threonine Kinase 16 (STK16) when JAK2 signaling is blocked. Pharmacological inhibition or silencing of STK16 significantly enhances the sensitivity of TNBC cells to JAK2 inhibition, while over-expression of STK16 alleviates the anti-tumor effect of JAK2-inhibitor. Mechanistically, elevated STK16 expression rescues the phosphorylation status and transcriptional activity of STAT3, as STK16 is able to directly catalyze the phosphorylation of STAT3 at ser-727 residue. Our data indicate that upon JAK2 inhibition, TNBC cells express STK16 to maintain STAT3 transcriptional activity, dual-inhibition of JAK2/STK16 offers a potential way to treat TNBC patients.
