Non-canonical HIPPO-MST1/2 promotes hyper-proliferation of pulmonary vascular cells through CDC20

HIPPO components mammalian Ste20-like protein kinases 1 and 2 (MST1/2) are well described growth suppressors. However, in pulmonary arterial hypertension (PAH), MST1/2 switch their roles and become pro-proliferative and pro-survival molecules, supporting hyper-proliferation of pulmonary artery (PA) smooth muscle cells (PASMCs) and adventitial fibroblasts (PAAFs), remodeling of small PAs, and pulmonary hypertension. Here, we report that MST1/2 promotes hyper-proliferation and apoptosis resistance of human PAH PASMCs and PAAFs by up-regulating cell division cycle protein 20 (CDC20), establishing novel link between HIPPO-MST1/2 and cell cycle regulation in PAH. AUTHORS CONTRIBUTIONS: conception and design of the work (EAG, SSP, TVK); acquisition, analysis, and interpretation of data (TD, IZ, LJ, SOO, AP, TA, DL, DG, JRG, PJW, HD, TK); drafting and editing the manuscript (EAG, SSP, TVK, JRG, PJW).

• Dey, T.
• Zhyvylo, I.
• Jiang, L.
• Olapoju, S. O.
• Pena, A.
• Avolio, T.
• Lin, D.
• Goncharov, D.
• Greenland, J. R.
• Wolters, P. J.
• DeLisser, H.
• Pullamsetti, S. S.
• Kudryashova, T. V.
• Goncharova, E. A.