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

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.

doi:10.1101/2025.04.03.646845

bioRxiv · 10.1101/2025.04.03.646845

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

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.

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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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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.. 2025-04-04. Non-canonical HIPPO-MST1/2 promotes hyper-proliferation of pulmonary vascular cells through CDC20. https://doi.org/10.1101/2025.04.03.646845

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