MLLT11/AF1q boosts oncogenic STAT3 activity through Src-PDGFR tyrosine kinase signaling.
Constitutive STAT3 activation by tyrosine phosphorylation is critical for cancer initiation, progression, invasion, and motility of carcinoma cells. We showed that AF1q is associated with STAT3 signaling in breast cancer cells. In xenograft models, enhanced AF1q expression activated STAT3 and promoted tumor growth and metastasis. The cytokine secretory phenotype of breast cancer cells with AF1q expression revealed expression of platelet-derived growth factor subunit B (PDGF-B). AF1q-induced PDGF-B stimulated motility, migration, and invasion. Further, AF1q-induced PDGFR signaling enhanced STAT3 activity through Src kinase activation, which could be blocked by the Srckinase inhibitor PP1or PDGFR inhibitor imatinib. In conclusion, we demonstrated that enhanced AF1q expression contributes to persistent and oncogenic pYSTAT3 levels in invasive carcinoma cells by activating Src kinase through activation of the PDGF-B/PDGFR cascade.
Therefore, AF1q plays an essential role as a cofactor in PDGF-B-driven STAT3 signaling.