Elucidating the role of a newly discovered mTOR-STAT3 pathway in regulating calcium-mediated apoptosis in breast cancer

The pro-oncogenic transcription STAT3 plays a multitude of roles during tumor transformation and progression. STAT3 canonical activity as a transcription factor is mainly exerted via its phosphorylation on Y705 (Y-P); in contrast, its phosphorylation on S727 (S-P) orchestrates transcription-independent features. Among the latters, we have recently described the ability of serine-phosphorylated STAT3 (S-P) to control ER Ca2+ release and Ca2+-mediated apoptosis in STAT3-dependent TNBC cells, via its localization to the ER/MAMs and interaction with the Ca2+ channel IP3R3, triggering its degradation. Our preliminary data indicate that STAT3 and mTOR interact within the ER in TNBC cells, and that STAT3 effects on IP3R3 degradation and apoptosis are inhibited by the pan-TOR inhibitor Torin-1 but not through mTORC1 inhibition via Rapamycin.