CDC2 Is an Important Driver of Vascular Smooth Muscle Cell Proliferation via FOXM1 and PLK1 in Pulmonary Arterial Hypertension
Open accessPublished version of a preprint
Abstract
A key feature of pulmonary arterial hypertension (PAH) is the hyperplastic proliferation exhibited by the vascular smooth muscle cells from patients (HPASMC). The growth inducers FOXM1 and PLK1 are highly upregulated in these cells. The mechanism by which these two proteins direct aberrant growth in these cells is not clear. Herein, we identify cyclin-dependent kinase 1 (CDK1), also termed cell division cycle protein 2 (CDC2), as having a primary role in promoting progress of the cell cycle leading to proliferation in HPASMC. HPASMC obtained from PAH patients and pulmonary arteries from Sugen/hypoxia rats were investigated for their expression of CDC2. Protein levels of CDC2 were much higher in PAH than in cells from normal donors. Knocking down FOXM1 or PLK1 protein expression with siRNA or pharmacological inhibitors lowered the cellular expression of CDC2 considerably. However, knockdown of CDC2 with siRNA or inhibiting its activity with RO-3306 did not reduce the protein expression of FOXM1 or PLK1. Expression of CDC2 and FOXM1 reached its maximum at G1/S, while PLK1 reached its maximum at G2/M phase of the cell cycle. The expression of other CDKs such as CDK2, CDK4, CDK6, CDK7, and CDK9 did not change in PAH HPASMC. Moreover, inhibition via Wee1 inhibitor adavosertib or siRNAs targeting Wee1, Myt1, CDC25A, CDC25B, or CDC25C led to dramatic decreases in CDC2 protein expression. Lastly, we found CDC2 expression at the RNA and protein level to be upregulated in pulmonary arteries during disease progression Sugen/hypoxia rats. In sum, our present results illustrate that the increased expression of FOXM1 and PLK1 in PAH leads directly to increased expression of CDC2 resulting in potentiated growth hyperactivity of PASMC from patients with pulmonary hypertension. Our results further suggest that the regulation of CDC2, or associated regulatory proteins, will prove beneficial in the treatment of this disease.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
This evidence supports multilevel regulation of the CDK1/cyclin B1 axis by MGF.
“This evidence supports multilevel regulation of the CDK1/cyclin B1 axis by MGF.”
From Mangiferin in human disease: Multifaceted mechanisms and applications (Review) (2026) · cites this paper as [57]
The Introduction (page unavailable) describes several mechanisms regulating the CDC2/CDK1–cyclin B complex, including phosphorylation and activation by CDC25. The Discussion (page unavailable) also describes multiple CDC2 regulators. Our copy does not mention MGF or show that MGF regulates this axis, so the MGF-specific conclusion is unsupported. (LLM, conf=0.80)
Experimental — accuracy not yet measuredMGF decreases CDK1/cyclin B1 activity, alters CDK1 phosphorylation, and engages ATR-dependent Chk1 activation in other tumor cell lines.
“This outcome is consistent with reports of decreased CDK1/cyclin B1 activity, altered phosphorylation of CDK1 with reduced activating phosphorylation and increased inhibitory phosphorylation, and engagement of checkpoint signaling, including ATR-dependent Chk1 activation, in other tumor cell lines exposed to MGF (56,57).”
From Mangiferin in human disease: Multifaceted mechanisms and applications (Review) (2026) · cites this paper as [57]
The Introduction describes activating and inhibitory phosphorylation of CDC2/cyclin B, but not changes caused by MGF. The paper’s Results concern pulmonary artery smooth muscle cells; searches for MGF, mangiferin, and ATR-dependent Chk1 activation found no passage addressing the claimed effects in tumor cell lines. No page numbers are available in our copy. (LLM, conf=0.78)
Experimental — accuracy not yet measuredAcross tumor cell systems, the functional consequence of MGF exposure remains G2/M arrest, with reduced proliferation and increased susceptibility to apoptosis.
“However, across tumor cell systems, the functional consequence remains G2/M arrest, with reduced proliferation and increased susceptibility to apoptosis.”
From Mangiferin in human disease: Multifaceted mechanisms and applications (Review) (2026) · cites this paper as [57]
The Discussion describes G2/M arrest with the CDC2 inhibitor RO-3306, not with MGF. The paper studies pulmonary-artery smooth muscle cells; searches for MGF and mangiferin found no passage addressing their effects on tumor-cell proliferation or apoptosis. The claimed outcome of MGF exposure therefore cannot be verified from this copy. (LLM, conf=0.78)
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Progressive Activation of CyclinB1-Cdk1 Coordinates Entry to Mitosis
Gavet, O., & Pines, J. (2010) · Developmental Cell · doi:10.1016/j.devcel.2010.02.013 · Cited by 849 · see citing works
Cellular and Molecular Basis of Pulmonary Arterial Hypertension
Morrell, N. W., Adnot, S., Archer, S. L., Dupuis, J., Jones, P. L., MacLean, M. R., McMurtry, I. F., Stenmark, K. R., Thistlethwaite, P. A., Weißmann, N., et al. (2009) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2009.04.018 · Cited by 818 · see citing works
FoxM1 is required for execution of the mitotic programme and chromosome stability
Laoukili, J., Kooistra, M. R. H., Brás, A., Kauw, J. J. W., Kerkhoven, R. M., Morrison, A. J., Clevers, H. C., & Medema, R. H. (2005) · Nature Cell Biology · doi:10.1038/ncb1217 · Cited by 808 · see citing works
Selective small-molecule inhibitor reveals critical mitotic functions of human CDK1
Vassilev, L. T., Tovar, C., Chen, S., Knezevic, D., Zhao, X., Sun, H., Heimbrook, D. C., & Chen, L. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0600447103 · Cited by 800 · see citing works
Mammalian cell-cycle regulation: several Cdks, numerous cyclins and diverse compensatory mechanisms
Satyanarayana, A., & Kaldis, P. (2009) · Oncogene · doi:10.1038/onc.2009.170 · Cited by 772 · see citing works
Ding, L., Cao, J., Lin, W.-S., Chen, H., Xiong, X., Ao, H., Yu, M., Lin, J., & Cui, Q. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21061960 · Cited by 634 · see citing works
Wang, I.-C., Chen, Y.-J., Hughes, D., Petrovic, V., Major, M. L., Park, H. J., Tan, Y., Ackerson, T., & Costa, R. H. (2005) · Molecular and Cellular Biology · doi:10.1128/mcb.25.24.10875-10894.2005 · Cited by 627 · see citing works
Bora and the Kinase Aurora A Cooperatively Activate the Kinase Plk1 and Control Mitotic Entry
Seki, A., Coppinger, J. A., Jang, C., Yates, J. R., & Fang, G. (2008) · Science · doi:10.1126/science.1157425 · Cited by 622 · see citing works
The decision to enter mitosis: feedback and redundancy in the mitotic entry network
Lindqvist, A., Rodríguez-Bravo, V., & Medema, R. H. (2009) · The Journal of Cell Biology · doi:10.1083/jcb.200812045 · Cited by 559 · see citing works
Anders, L., Ke, N., Hydbring, P., Choi, Y. J., Widlund, H. R., Chick, J. M., Zhai, H., Vidal, M., Gygi, S. P., Braun, P., et al. (2011) · Cancer Cell · doi:10.1016/j.ccr.2011.10.001 · Cited by 543 · see citing works
Regulatory phosphorylation of the p34cdc2 protein kinase in vertebrates.
Norbury, C. J., Blow, J. J., & Nurse, P. (1991) · The EMBO Journal · doi:10.1002/j.1460-2075.1991.tb04896.x · Cited by 503 · see citing works
Human Wee1 kinase inhibits cell division by phosphorylating p34cdc2 exclusively on Tyr15.
McGowan, C. H., & Russell, P. R. (1993) · The EMBO Journal · doi:10.1002/j.1460-2075.1993.tb05633.x · Cited by 495 · see citing works
Platelet-derived Growth Factor Expression and Function in Idiopathic Pulmonary Arterial Hypertension
Perros, F., Montani, D., Dorfmüller, P., Durand–Gasselin, I., Tchérakian, C., Pavec, J. L., Mazmanian, M. G., Fadel, É., Mussot, S., Mercier, O. M., et al. (2008) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.200707-1037oc · Cited by 471 · see citing works
Yuan, J. X.-J., Aldinger, A. M., Juhaszova, M., Wang, J., Conte, J. V., Gaine, S., Orens, J. B., & Rubin, L. J. (1998) · Circulation · doi:10.1161/01.cir.98.14.1400 · Cited by 424 · see citing works
Coleman, T. R., & Dunphy, W. G. (1994) · Current Opinion in Cell Biology · doi:10.1016/0955-0674(94)90060-4 · Cited by 414 · see citing works
Diril, M. K., Ratnacaram, C. K., Padmakumar, V. C., Du, T., Wasser, M., Coppola, V., Tessarollo, L., & Kaldis, P. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1115201109 · Cited by 385 · see citing works
Liu, F., Stanton, J. J., Wu, Z., & Piwnica-Worms, H. M. (1997) · Molecular and Cellular Biology · doi:10.1128/mcb.17.2.571 · Cited by 378 · see citing works
Relevant Issues in the Pathology and Pathobiology of Pulmonary Hypertension
Tuder, R., Archer, S., Dorfmüller, P., Erzurum, S., Guignabert, C., Michelakis, E., Rabinovitch, M., Schermuly, R., Stenmark, K., & Morrell, N. (2013) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2013.10.025 · Cited by 368 · see citing works
Yang, X., Long, L., Southwood, M. R., Rudarakanchana, N., Upton, P. D., Jeffery, T. K., Atkinson, C., Chen, H., Trembath, R. C., & Morrell, N. W. (2005) · Circulation Research · doi:10.1161/01.res.0000166926.54293.68 · Cited by 364 · see citing works
Fu, Z., Malureanu, L. A., Huang, J., Wang, W., Li, H., van Deursen, J. M., Tindall, D. J., & Chen, J. (2008) · Nature Cell Biology · doi:10.1038/ncb1767 · Cited by 357 · see citing works
Plk1 promotes nuclear translocation of human Cdc25C during prophase
Toyoshima, F., Taniguchi, E., & Nishida, E. (2002) · EMBO Reports · doi:10.1093/embo-reports/kvf069 · Cited by 338 · see citing works
Nakajima, H., Toyoshima, F., Taniguchi, E., & Nishida, E. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.c300126200 · Cited by 338 · see citing works
Savai, R., Al-tamari, H. M., Sedding, D., Kojonazarov, B. K., Muecke, C., Teske, R., Capecchi, M. R., Weißmann, N., Grimminger, F., Seeger, W., et al. (2014) · Nature Medicine · doi:10.1038/nm.3695 · Cited by 276 · see citing works
The transcription factor FOXM1 is a cellular target of the natural product thiostrepton
Hegde, N. S., Sanders, D. A., Rodriguez, R., & Balasubramanian, S. (2011) · Nature Chemistry · doi:10.1038/nchem.1114 · Cited by 269 · see citing works
Major, M. L., Lepe, R., & Costa, R. H. (2004) · Molecular and Cellular Biology · doi:10.1128/mcb.24.7.2649-2661.2004 · Cited by 267 · see citing works
The Cancer Paradigm of Severe Pulmonary Arterial Hypertension
Rai, P. R., Cool, C. D., KING, J. A. C., Stevens, T., Burns, N., Winn, R. A., Kasper, M. E., & Voelkel, N. F. (2008) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.200709-1369pp · Cited by 258 · see citing works
Raf/MEK/MAPK signaling stimulates the nuclear translocation and transactivating activity of FOXM1c
Richard, Y. M., Tong, T. H. K., Cheung, A. M. S., Tsang, A. C. C., Leung, W. Y., & Yao, K. (2005) · Journal of Cell Science · doi:10.1242/jcs.01657 · Cited by 231 · see citing works
Cyclin-dependent kinase (CDK) phosphorylation destabilizes somatic Wee1 via multiple pathways
Watanabe, N., Arai, H., Iwasaki, J.-I., Shiina, M., Ogata, K., Hunter, T. R., & Osada, H. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0500410102 · Cited by 229 · see citing works
Chen, X. X., Müller, G. A., Quaas, M., Fischer, M., Han, N., Stutchbury, B., Sharrocks, A. D., & Engeland, K. (2012) · Molecular and Cellular Biology · doi:10.1128/mcb.00881-12 · Cited by 226 · see citing works
Goncharov, D. A., Kudryashova, T. V., Ziai, H., Ihida‐Stansbury, K., DeLisser, H. M., Krymskaya, V. P., Tuder, R. M., Kawut, S. M., & Goncharova, E. A. (2013) · Circulation · doi:10.1161/circulationaha.113.004581 · Cited by 202 · see citing works
The cancer theory of pulmonary arterial hypertension
Boucherat, O., Vitry, G., Trinh, I., Paulin, R., Provencher, S., & Bonnet, S. (2017) · Pulmonary Circulation · doi:10.1177/2045893217701438 · Cited by 200 · see citing works
PLK1 Activation in Late G2 Sets Up Commitment to Mitosis
Gheghiani, L., Loew, D., Lombard, B., Mansfeld, J., & Gavet, O. (2017) · Cell Reports · doi:10.1016/j.celrep.2017.05.031 · Cited by 200 · see citing works
New mechanisms of pulmonary arterial hypertension: role of Ca2+signaling
Kuhr, F., Smith, K. A., Song, M., Levitan, I., & Yuan, J. X. ‐. (2012) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00944.2011 · Cited by 184 · see citing works
Cdc25 and Wee1: analogous opposites?
Perry, J. A., & Kornbluth, S. A. (2007) · Cell Division · doi:10.1186/1747-1028-2-12 · Cited by 175 · see citing works
Smooth muscle cell progenitors are primed to muscularize in pulmonary hypertension
Sheikh, A. Q., Misra, A., Rosas, I. O., Adams, R. H., & Greif, D. M. (2015) · Science Translational Medicine · doi:10.1126/scitranslmed.aaa9712 · Cited by 174 · see citing works
Wells, N. J., Watanabe, N., Tokusumi, T., Jiang, W. B., Verdecia, M. A., & Hunter, T. R. (1999) · Journal of Cell Science · doi:10.1242/jcs.112.19.3361 · Cited by 165 · see citing works
Dai, Z., Zhu, M. M., Peng, Y., Jin, H., Machireddy, N., Qian, Z., Zhang, X., & Zhao, Y. (2018) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.201709-1835oc · Cited by 164 · see citing works
Stenmark, K. R., Frid, M. G., Graham, B. B., & Tuder, R. M. (2018) · Cardiovascular Research · doi:10.1093/cvr/cvy004 · Cited by 161 · see citing works
Ferguson, A. M., White, L. S., Donovan, P. J., & Piwnica-Worms, H. M. (2005) · Molecular and Cellular Biology · doi:10.1128/mcb.25.7.2853-2860.2005 · Cited by 160 · see citing works
van der Feen, D. E., Kurakula, K., Tremblay, È., Boucherat, O., Bossers, G. P. L., Szulcek, R., Bourgeois, A., Lampron, M.-C., Habbout, K., Martineau, S., et al. (2019) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.201812-2275oc · Cited by 157 · see citing works
Phylogenetic analysis of CDK and cyclin proteins in premetazoan lineages
Cao, L., Chen, F., Yang, X., Xu, W., Xie, J., & Yu, L. (2014) · BMC Evolutionary Biology · doi:10.1186/1471-2148-14-10 · Cited by 144 · see citing works
Kudryashova, T. V., Goncharov, D. A., Pena, A. Z., Kelly, N. J., Vanderpool, R. R., Baust, J., Kobir, A., Shufesky, W. J., Mora, A. L., Morelli, A. E., et al. (2016) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.201510-2003oc · Cited by 137 · see citing works
FoxM1 is a downstream target and marker of HER2 overexpression in breast cancer
Lam (2009) · International Journal of Oncology · doi:10.3892/ijo_00000313 · Cited by 124 · see citing works
Role of apoptosis in pulmonary hypertension: From experimental models to clinical trials
Jurasz, P., Courtman, D. W., Babaie, S., & Stewart, D. J. (2010) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2009.12.006 · Cited by 124 · see citing works
Cyclin A-cdk1-Dependent Phosphorylation of Bora Is the Triggering Factor Promoting Mitotic Entry
Vigneron, S., Sundermann, L., Labbé, J., Pintard, L., Radulescu, O., Castro, A., & Lorca, T. (2018) · Developmental Cell · doi:10.1016/j.devcel.2018.05.005 · Cited by 118 · see citing works
Fernandez, R. A., Wan, J., Song, S., Smith, K. A., Gu, Y., Tauseef, M., Tang, H., Makino, A., Mehta, D., & Yuan, J. X. ‐. (2015) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00202.2014 · Cited by 117 · see citing works
Krymskaya, V. P., Snow, J., Cesarone, G., Khavin, I., Goncharov, D. A., Lim, P. N., Veasey, S. C., Ihida‐Stansbury, K., Jones, P. L., & Goncharova, E. A. (2011) · The FASEB Journal · doi:10.1096/fj.10-175018 · Cited by 116 · see citing works
Recapitulation of Developing Artery Muscularization in Pulmonary Hypertension
Sheikh, A. Q., Lighthouse, J. K., & Greif, D. M. (2014) · Cell Reports · doi:10.1016/j.celrep.2014.01.042 · Cited by 112 · see citing works
Gabrielli, B. G., Clark, J. M., McCormack, A. K., & Ellem, K. A. O. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.45.28607 · Cited by 112 · see citing works
Chen, Y.-J., Dominguez‐Brauer, C., Wang, Z., Asara, J. M., Costa, R. H., Tyner, A. L., Lau, L. F., & Raychaudhuri, P. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.007997 · Cited by 106 · see citing works
DNA Damage and Pulmonary Hypertension
Ranchoux, B., Meloche, J., Paulin, R., Boucherat, O., Provencher, S., & Bonnet, S. (2016) · International Journal of Molecular Sciences · doi:10.3390/ijms17060990 · Cited by 105 · see citing works
Andrés, V. (2004) · Cardiovascular Research · doi:10.1016/j.cardiores.2004.02.009 · Cited by 104 · see citing works
Human Primary Lung Endothelial Cells in Culture
COMHAIR, S. A. A., Xu, W., Mavrakis, L. A., Aldred, M. A., Asosingh, K., & ERZURUM, S. C. (2012) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/rcmb.2011-0416te · Cited by 101 · see citing works
SuHx rat model: partly reversible pulmonary hypertension and progressive intima obstruction
de Raaf, M. A., Schalij, I., Gomez‐Arroyo, J. G., Rol, N., Happé, C. M., de Man, F. S., Noordegraaf, A. V., Westerhof, N., Voelkel, N. F., & Bogaard, H. J. (2014) · European Respiratory Journal · doi:10.1183/09031936.00204813 · Cited by 97 · see citing works
Targeting cyclin-dependent kinases for the treatment of pulmonary arterial hypertension
Weiß, A., Neubauer, M. C., Yerabolu, D., Kojonazarov, B. K., Schlueter, B. C., Neubert, L., Jonigk, D. D., Baal, N., Ruppert, C., Dorfmüller, P., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-10135-x · Cited by 94 · see citing works
Cell Autonomous and Non-cell Autonomous Regulation of SMC Progenitors in Pulmonary Hypertension
Sheikh, A. Q., Saddouk, F. Z., Ntokou, A., Mazurek, R., & Greif, D. M. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.03.043 · Cited by 93 · see citing works
A critical role for p130Cas in the progression of pulmonary hypertension in humans and rodents.
Tu, L., de Man, F. S., Girerd, B., Huertas, A., Chaumais, M., Lecerf, F., François, C., Perros, F., Dorfmüller, P., Fadel, E., et al. (2012) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.201202-0309oc · Cited by 87 · see citing works
FOXM1 promotes pulmonary artery smooth muscle cell expansion in pulmonary arterial hypertension
Bourgeois, A., Lambert, C., Habbout, K., Ranchoux, B., Paquet-Marceau, S., Trinh, I., Breuils‐Bonnet, S., Paradis, R., Nadeau, V., Paulin, R., et al. (2017) · Journal of Molecular Medicine · doi:10.1007/s00109-017-1619-0 · Cited by 85 · see citing works
CDK1 inhibition sensitizes normal cells to DNA damage in a cell cycle dependent manner
Prevo, R., Pirovano, G., Puliyadi, R., Herbert, K. J., Rodríguez‐Berriguete, G., O’Docherty, A., Greaves, W., McKenna, W. G., & Higgins, G. S. (2018) · Cell Cycle · doi:10.1080/15384101.2018.1491236 · Cited by 82 · see citing works
Wang, I., Zhang, Y., Snyder, J. E., Sutherland, M. J., Burhans, M. S., Shannon, J. M., Park, H. J., Whitsett, J. A., & Kalinichenko, V. V. (2010) · Developmental Biology · doi:10.1016/j.ydbio.2010.08.027 · Cited by 69 · see citing works
Targeting Cyclin-Dependent Kinases for Treatment of Gynecologic Cancers
Lin, Z. P., Zhu, Y.-L., & Ratner, E. (2018) · Frontiers in Oncology · doi:10.3389/fonc.2018.00303 · Cited by 68 · see citing works
Inhibitory Phosphorylation of Cyclin-Dependent Kinase 1 as a Compensatory Mechanism for Mitosis Exit
Chow, J. P. H., Poon, R. Y. C., & Ma, H. T. (2011) · Molecular and Cellular Biology · doi:10.1128/mcb.00891-10 · Cited by 64 · see citing works
Unmasking the Redundancy Between Cdk1 and Cdk2 at G2 Phase in Human Cancer Cell Lines
L’Italien, L., Tanudji, M., Russell, L., & Schebye, X. M. (2006) · Cell Cycle · doi:10.4161/cc.5.9.2721 · Cited by 63 · see citing works
Targeting cell motility in pulmonary arterial hypertension
Paulin, R., Meloche, J., Courboulin, A., Lambert, C. M., Haromy, A., Courchesne, A., Bonnet, P., Provencher, S., Michelakis, E. D., & Bonnet, S. (2013) · European Respiratory Journal · doi:10.1183/09031936.00181312 · Cited by 61 · see citing works
The Emerging Role of Polo-Like Kinase 1 in Epithelial-Mesenchymal Transition and Tumor Metastasis
Fu, Z., & Wen, D. (2017) · Cancers · doi:10.3390/cancers9100131 · Cited by 58 · see citing works
Gorlick, R. G., Kolb, E. A., Keir, S. T., Maris, J. M., Reynolds, C. P., Kang, M. H., Carol, H., Lock, R. B., Billups, C. A., Kurmasheva, R. T., et al. (2013) · Pediatric Blood & Cancer · doi:10.1002/pbc.24616 · Cited by 57 · see citing works
Bourgeois, A., Bonnet, S., Breuils‐Bonnet, S., Habbout, K., Paradis, R., Tremblay, È., Lampron, M.-C., Orcholski, M. E., Potus, F., Bertero, T., et al. (2019) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.119.312537 · Cited by 48 · see citing works
The FOXM1-PLK1 axis is commonly upregulated in oesophageal adenocarcinoma
Dibb, M. J., Han, N., Choudhury, J., Hayes, S. J., Valentine, H. R., West, C., Ang, Y. S., & Sharrocks, A. D. (2012) · British Journal of Cancer · doi:10.1038/bjc.2012.424 · Cited by 45 · see citing works
Novel Interactions between FOXM1 and CDC25A Regulate the Cell Cycle
Sullivan, C., Liu, Y., Shen, J., Adam, C., Christina, N., Hock, J. M., & Li, X. (2012) · PLoS ONE · doi:10.1371/journal.pone.0051277 · Cited by 42 · see citing works
Zhang, J., Yuan, C., Wu, J., Elsayed, Z., & Fu, Z. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.m114.634386 · Cited by 41 · see citing works
Wilson, J. L., Yu, J., Taylor, L., & POLGAR, P. R. (2015) · PLoS ONE · doi:10.1371/journal.pone.0123662 · Cited by 38 · see citing works
Self-citationSmooth muscle cell-specific FoxM1 controls hypoxia-induced pulmonary hypertension
Dai, J., Zhou, Q., Tang, H., Chen, T., Li, J., Raychaudhuri, P., Yuan, J. X. ‐., & Zhou, G. (2018) · Cellular Signalling · doi:10.1016/j.cellsig.2018.08.003 · Cited by 37 · see citing works
Li, H., Wang, H., Sun, Z., Guo, Q., Shi, H., & Jia, Y. (2017) · Bioscience Reports · doi:10.1042/bsr20170852 · Cited by 37 · see citing works
Chen, Y., Liu, Y., Ni, H., Ding, C., Zhang, X., & Zhang, Z. (2017) · International Journal of Oncology · doi:10.3892/ijo.2017.4094 · Cited by 33 · see citing works
Smooth Muscle Phenotype in Idiopathic Pulmonary Hypertension: Hyper-Proliferative but not Cancerous
Perros, F., Sentenac, P., Boulate, D., Manaud, G., Kotsimbos, T. C., Lecerf, F., Lamrani, L., Fadel, É., Mercier, O. M., Londoño‐Vallejo, A., et al. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20143575 · Cited by 32 · see citing works
Yu, J., Taylor, L., Wilson, J. L., COMHAIR, S. A. A., ERZURUM, S. C., & POLGAR, P. R. (2012) · Journal of Cellular Physiology · doi:10.1002/jcp.24132 · Cited by 30 · see citing works
Self-citationStudy of the docking-dependent PLK1 phosphorylation of the CDC25B phosphatase
Lobjois, V., Froment, C., Braud, E., Grimal, F., Burlet‐Schiltz, O., Ducommun, B., & Bouché, J. (2011) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2011.05.110 · Cited by 27 · see citing works
WAC Promotes Polo-like Kinase 1 Activation for Timely Mitotic Entry
Qi, F., Chen, Q., Chen, H., Yan, H., Chen, B., Xiang, X., Liang, C., Yi, Q., Zhang, M., Cheng, H., et al. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.06.087 · Cited by 26 · see citing works
Kudryashova, T. V., Shen, Y., Pena, A. Z., Cronin, E., Okorie, E., Goncharov, D. A., & Goncharova, E. A. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19102957 · Cited by 26 · see citing works
Overexpression of Plk1 promotes malignant progress in human esophageal squamous cell carcinoma
Zhao, C., Gong, L., Li, W., & Chen, L.-M. (2009) · Journal of Cancer Research and Clinical Oncology · doi:10.1007/s00432-009-0630-4 · Cited by 26 · see citing works
Yu, J., Wilson, J. L., Taylor, L., & POLGAR, P. R. (2014) · Journal of Cellular Biochemistry · doi:10.1002/jcb.24987 · Cited by 23 · see citing works
Self-citationBi, S., Wei, Q., Zhao, Z., Chen, L., Wang, C., & Xie, S. (2019) · Frontiers in Pharmacology · doi:10.3389/fphar.2019.00864 · Cited by 20 · see citing works
Wu, K., Tang, H., Lin, R., Carr, S. G., Wang, Z., Babicheva, A., Ayon, R. J., Jain, P., Xiong, M., Rodriguez, M., et al. (2020) · Pulmonary Circulation · doi:10.1177/2045894020948470 · Cited by 20 · see citing works
Wilson, J. L., Wang, L., Zhang, Z., Hill, N. S., & POLGAR, P. R. (2019) · PLoS ONE · doi:10.1371/journal.pone.0221728 · Cited by 17 · see citing works
Self-citationWilson, J. L., Warburton, R. R., Taylor, L., Toksoz, D., Hill, N. S., & POLGAR, P. R. (2018) · PLoS ONE · doi:10.1371/journal.pone.0195780 · Cited by 16 · see citing works
Self-citationYu, J., Rupasinghe, C. N., Wilson, J. L., Taylor, L., Rahimi, N., Mierke, D. F., & POLGAR, P. R. (2014) · Chemical Biology & Drug Design · doi:10.1111/cbdd.12446 · Cited by 16 · see citing works
Self-citationSevere Pulmonary Arterial Hypertension
Humbert, M. J. C., & Hoeper, M. M. (2008) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.200806-867ed · Cited by 13 · see citing works
Yu, J., Taylor, L., Mierke, D. F., Berg, E. A., Shia, M. A., Fishman, J. B., Sallum, C. O., & POLGAR, P. R. (2010) · Chemical Biology & Drug Design · doi:10.1111/j.1747-0285.2010.00985.x · Cited by 12 · see citing works
Self-citationWilson, J. L., Rupasinghe, C. N., Usheva, A., Warburton, R. R., Kaplan, C., Taylor, L., Hill, N. S., Mierke, D. F., & POLGAR, P. R. (2015) · PubMed · Cited by 7 · see citing works
Self-citationSallum, C. O., Wilson, J. L., Rupasinghe, C. N., Berg, E. A., Yu, J., Green, D. S., Taylor, L., Mierke, D. F., & POLGAR, P. R. (2012) · Chemical Biology & Drug Design · doi:10.1111/j.1747-0285.2012.01405.x · Cited by 6 · see citing works
Self-citation
Flagged first, then by citations
1 of the 91 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Shi, Z., Tian, L., Qiang, T., Li, J., Xing, Y. Q., Ren, X., Liu, C., & Liang, C. (2022) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.1c02064 · Cited by 68 · see citing works
Xiao, F., Zhang, R., & Wang, L. (2022) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2022.913904 · Cited by 19 · see citing works
Zhai, C., Zhang, N., Wang, J., Cao, M., Luan, J., Liu, H., Zhang, Q., Zhu, Y., Xue, Y., & Li, S. (2022) · Lung · doi:10.1007/s00408-022-00569-4 · Cited by 12 · see citing works
Chen, Z., Chai, S., Ding, Y., Pang, K., Dong, T., Dai, D., Wang, J., Wang, S., & Liu, S. (2025) · Microbiology Spectrum · doi:10.1128/spectrum.00045-25 · Cited by 12 · see citing works
Transcriptome wide changes in long noncoding RNAs in diabetic ischemic heart disease
Kumar, A., Natarajaseenivasan, S. M., Nisini, N., Lee, T. A., Kyriazis, I. D., de Lucia, C., Piedepalumbo, M., Roy, R., Uchida, S., Drosatos, K., et al. (2024) · Cardiovascular Diabetology · doi:10.1186/s12933-024-02441-6 · Cited by 7 · see citing works
Song, S., Zhang, X., Huang, Z., Zeng, L., Cai, F., Wang, T., Song, Y., Guo, J., Li, M., Liu, C., et al. (2025) · Cell Death and Differentiation · doi:10.1038/s41418-025-01609-1 · Cited by 6 · see citing works
Targets for Renal Carcinoma Growth Control Identified by Screening FOXD1 Cell Proliferation Pathways
Bond, K., Sims‐Lucas, S., & Oxburgh, L. H. (2022) · Cancers · doi:10.3390/cancers14163958 · Cited by 5 · see citing works
Alur, V. C., Vastrad, B. M., Raju, V., Vastrad, C. M., & Kotrashetti, S. (2024) · Middle East Fertility Society Journal · doi:10.1186/s43043-024-00212-7 · Cited by 4 · see citing works
Zhang, X., Yang, Z., Li, X., Liu, X., Wang, X., Qiu, T., Wang, Y., Li, T., & Li, Q. (2022) · Frontiers in Genetics · doi:10.3389/fgene.2022.823769 · Cited by 4 · see citing works
Mangiferin in human disease: Multifaceted mechanisms and applications (Review)
Dai, Y., Huang, Q., Tan, M., Wang, Z., Jiang, C., Liu, Z., Zhang, S., & Song, S. (2026) · International Journal of Molecular Medicine · doi:10.3892/ijmm.2026.5736 · Cited by 3 · see citing works
“…with reports of decreased cdK1/cyclin B1 activity, altered phosphoryla‑ tion of cdK1 with reduced activating phosphorylation and increased inhibitory phosphorylation, and engagement of checkpoint signaling, including ATR‑dependent chk1 activa‑ tion, in other tumor cell lines exposed to MGF (56,57).”
Wennersten, S. A., Wang, H., Franklin, J. L., & Nanda, V. (2025) · Vascular Pharmacology · doi:10.1016/j.vph.2025.107555 · Cited by 2 · see citing works
Li, Y., Liu, S., Wei, X., Zhang, R., Zhang, Y., & Guo, C. (2022) · Current Computer - Aided Drug Design · doi:10.2174/1573409918666220817100959 · Cited by 2 · see citing works
Wang, Y., Chi, Y., Zhu, C., Zhang, Y., Li, K., Chen, J., Jiang, X., Chen, K., & Li, S. (2024) · Scientific Reports · doi:10.1038/s41598-024-52742-9 · Cited by 2 · see citing works
Activation of PBK by Gal-3 contributes to pulmonary artery hypertension by promoting PRC1 activation
Zhang, J., Liu, J., Chen, Y., Chen, H., Meng, Y., Wang, Y., Qiu, Y., Hu, H., Shi, W., & Li, M. (2026) · Respiratory Research · doi:10.1186/s12931-026-03534-4 · Cited by 1 · see citing works
Ferrari, R., Cong, G., Chattopadhyay, A., Xie, B., Assaf, E., Morder, K. M., Calderon, M. J., Watkins, S. C., & Sachdev, U. (2022) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2022.03.161 · Cited by 1 · see citing works
Vastrad, B. M., & Vastrad, C. M. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.06.08.495272 · Cited by 1 · see citing works
Vastrad, B. M., & Vastrad, C. M. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.12.29.522191 · Cited by 1 · see citing works
Huang, W., Li, J.-X., Huang, Z., He, R., Chen, S., Li, G., Li, D., Tang, Y.-L., Tang, D., Zeng, J., et al. (2022) · Research Square · doi:10.21203/rs.3.rs-1199894/v1
Vastrad, B. M., & Vastrad, C. M. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.03.17.484749
Effect of JAK Inhibitors on IL-6-Induced Smooth Muscle Cell Function in Human Pulmonary ArteriesPreprint
Yan, F., Fan, G., Peng, Y., & Zhang, R. (2022) · SSRN Electronic Journal · doi:10.2139/ssrn.4192566
Machine Learning Discoveries of FOXM1-X Synergy in ETC-1922159 Treated Colorectal Cancer CellsPreprint
Sinha, S. (2025) · SSRN Electronic Journal · doi:10.2139/ssrn.5124535
Yang, W., Li, Q., Tong, T., Ye, W., & Wei, W. (2026) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.70563
- Authors
- Pal-Ghosh, R., Xue, D., Warburton, R., Hill, N., Polgar, P., & Wilson, J. L.
- Affiliations
- Tupper Research Institute and Pulmonary, Critical Care, and Sleep Division, Tufts Medical Center, Boston, MA 02111, USA
- Tufts Medical Center (US)
- Corresponding author
- Wilson, Jamie L.
- Venue
- International Journal of Molecular Sciences
- Publisher
- MDPI AG
- Published
- 2021-06-28
- Volume
- 22
- Issue
- 13
- Pages
- 6943
- ISSN
- 1422-0067 (ISSN-L)
- PMC
- PMC8268698
- OpenAlex
- W3173683284
- Cited by
- 22
- References
- 91
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 3 · 2023: 1 · 2022: 12
- FWCI
- 2.76
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- International Journal of Molecular Sciences (publishedVersion, cc-by)
- Preprints.org (acceptedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Heart, Lung, and Blood Institute (HL133796)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Pulmonary Hypertension Research and Treatments
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Health Sciences › Medicine › Genetics › Vascular Anomalies and Treatments
- Keywords
- pulmonary arterial hypertension, vascular smooth muscle cell proliferation, cdc2, cyclin-dependent kinase 1, FOXM1, PLK1, cell cycle regulation, WEE1, Sugen/hypoxia rat model, cyclin-dependent kinase inhibitors, adavosertib, Cdc25 phosphatase
- MeSH terms
- Forkhead Box Protein M1, Pulmonary Arterial Hypertension, Polo-Like Kinase 1, Animals, Cell Cycle, Humans, Male, Muscle, Smooth, Vascular, Proto-Oncogene Proteins, CDC2 Protein Kinase, Rats, Sprague-Dawley, Protein Serine-Threonine Kinases, Cell Cycle Proteins, Cell Proliferation, Rats, Vascular Remodeling
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
