CCN5/WISP-2 promotes growth arrest of triple-negative breast cancer cells through accumulation and trafficking of p27(Kip1) via Skp2 and FOXO3a regulation.

摘要: The matricellular protein CCN5/WISP-2 represents a promising target in triple-negative breast cancer (TNBC) because treatment or induced activation of CCN5 TNBC cells promotes cell growth arrest at the G0/G1 phase, reduces proliferation and delays tumor xenograft model. Our studies found that p27(Kip1) suppressor is upregulated relocalized to nucleus from cytoplasm by these two events (upregulation relocalization p27(Kip1)) are critical for CCN5-induced inhibition cells. In absence CCN5, resides mostly cytoplasm, which associated with aggressive nature Mechanistically, inhibits Skp2 expression, seems stabilize On other hand, also recruits FOXO3a mediate transcriptional regulation p27(Kip1). recruitment achieved induction its expression activity through shifting nucleus. data indicate blocks PI3K/AKT signaling dephosphorylate S318, S253 Thr32 nuclear FOXO3a. Moreover, α6β1 receptors diminishes action on Collectively, suggest effectively accumulation trafficking via regulation, thus, may have therapeutic potential kill TNBC.