MASTL is a mitotic accelerator with an emerging role in
breast cancer progression. However, the mechanisms behind its oncogenicity remain largely unknown. Here, we identify a previously unknown role and eminent expression of MASTL in stem cells. MASTL staining from a large
breast cancer patient cohort indicated a significant association with β3
integrin, an established mediator of
breast cancer stemness. MASTL silencing reduced OCT4 levels in human pluripotent stem cells and OCT1 in
breast cancer cells. Analysis of the cell-surface
proteome indicated a strong link between MASTL and the regulation of TGF-β receptor II (
TGFBR2), a key modulator of TGF-β signaling. Overexpression of wild-type and
kinase-dead MASTL in normal mammary epithelial cells elevated
TGFBR2 levels. Conversely, MASTL depletion in
breast cancer cells attenuated
TGFBR2 levels and downstream signaling through SMAD3 and AKT pathways. Taken together, these results indicate that MASTL supports stemness regulators in pluripotent and cancerous stem cells.