Autophagy promotes triple negative breast cancer metastasis via YAP nuclear localization

The triple-negative breast cancer (TNBC) subtype is the most aggressive form of invasive breast cancer. Although autophagy is critical to the progression of TNBC, the mechanism of autophagy in regulating the metastatic potential of TNBC still remains unclear. Recently, the effector of the Hippo signaling pathway yes-associated protein (YAP) was shown to promote autophagy. To investigate autophagy regulation in YAP signaling in the context of cancer metastasis, we performed profiling analysis of YAP signaling, YAP subcellular localization, autophagosome formation and cell invasiveness in TNBC cell lines (MDA-MB-231 and Hs 578T) versus estrogen receptor (ER) positive breast cancer cell line MCF7. Our results showed that YAP transcriptional and protein expression was significantly upregulated in TNBC. When we triggered autophagy response in TNBC, YAP translocated into the nucleus and the expression of YAP target gene ankyrin repeat domain 1 (ANKRD1) increased remarkably. The correlation between autophagy response and YAP expression in TNBC was confirmed at the single-cell level. Furthermore, the inhibition of YAP nuclear entry greatly impeded the migration and invasion of TNBC cells while it did not affect the mobility of ER positive breast cancer cells. Therefore, this research established the autophagy-YAP-metastasis axis in TNBC and sheds light on the application of targeting YAP for TNBC therapeutics.