A forceful connection: mechanoregulation of oncogenic YAP

Abstract

The Yes‐associated protein (YAP) is an important transcriptional co‐activator that mediates the cellular response to mechanical and cytoskeletal cues. In two recent papers published in The EMBO Journal, Dae‐Sik Lim and colleagues show how YAP activity affects cancer formation and metastasis via a crosstalk with myocardin‐related transcription factors (MRTFs; Kim et al, 2017) and SKP2‐dependent cell cycle progression (Jang et al, 2017).

The role of RAS oncogenes in controlling epithelial mechanics

“…RAS-ERK signalling also crosstalks with the YAP/TAZ pathway. YAP/TAZ transcriptional regulators play critical roles in mechanotransduction [ 45 ], and their role in cancer development and progression has been widely studied and previously reviewed [ 46 , 47 ]. YAP/TAZ are transcriptional coactivators of the Hippo pathway that shuttle between the cell cytoplasm and nucleus in response to mechanical cues, such as the activation of Rho and cortical tension [ 45 ].…”

The Hippo Signaling Pathway in Cancer: A Cell Cycle Perspective

“…A recent study demonstrated that YAP associates with YY1 and EZH2 on the genome to inhibit p27 expression at the transcriptional level [ 208 ]. Additionally, in response to mechanical cues, YAP elevates the transcription of ubiquitin ligase Skp2, which subsequently forms a complex with Skp1-Cullin-1-F-box (SCF) to target p21 and p27 for proteasomal degradation [ 209 , 210 ]. By collaborating with FOXM1, an essential cell cycle transcription factor that promotes G1/S progression in part by increasing the Skp2-mediated degradation of p21 and p27, YAP further prompts E2F-mediated gene expression [ 151 , 211 ].…”