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

Tapan Dey; Iryna Zhyvylo; Lifeng Jiang; Samuel O Olapoju; Andressa Z. Pena; Theodore Avolio; Derek Lin; Dmitry A. Goncharov; John R. Greenland; Paul J. Wolters; Horace Michael DeLisser; Soni Savai Pullamsetti; Tatiana V. Kudryashova; Elena A. Goncharova

doi:10.1165/rcmb.2025-0238le

Cell BiologyAmerican Journal of Respiratory Cell and Molecular BiologySep 5, 2025

Peer-reviewed journal article

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

Tapan Dey iD, Iryna Zhyvylo iD, Lifeng Jiang iD, Samuel O Olapoju iD, Andressa Z. Pena iD, Theodore Avolio, Derek Lin, Dmitry A. Goncharov iD, John R. Greenland iD, Paul J. Wolters iD, Horace Michael DeLisser iD, Soni Savai Pullamsetti iD, Tatiana V. Kudryashova iD, Elena A. Goncharova iD

Abstract

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 Contributionsconception 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).

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