Breast cancer mortality is primarily due to tumor recurrence. In a study reported in Cancer Discovery, Feng and colleagues found that the suppressor of cytokine signaling protein SPSB1 is spontaneously upregulated in mammary tumor recurrence and is both necessary and sufficient to promote tumor recurrence in mouse models. SPSB1 was found to promote recurrence by protecting cells from apoptosis caused by HER2/neu pathway inhibition or chemotherapy.
This effect was associated with potentiation of c-MET signaling by SPSB1, with preexisting SPSB1-overexpressing tumor cells being selected for after HER2/neu downregulation. SPSB1 expression was found to be positively correlated with c-MET activity in human breast cancers, with an increased risk of relapse being dependent on c-MET activity.
The investigators concluded, “This study identifies SPSB1 as a critical mediator of breast cancer recurrence, suggests activation of the SPSB1–c-MET pathway as an important mechanism of therapeutic resistance in breast cancers, and emphasizes that pharmacologic targets for recurrence may be unique to this stage of tumor progression.” ■
Feng Y, et al: Cancer Discov 4:790-803, 2014.