PIM2 Promotes the Development of Ovarian Endometriosis by Enhancing Glycolysis and Fibrosis.
Endometriosis
Fibrosis
Glycolysis
PIM2
PKM2
Journal
Reproductive sciences (Thousand Oaks, Calif.)
ISSN: 1933-7205
Titre abrégé: Reprod Sci
Pays: United States
ID NLM: 101291249
Informations de publication
Date de publication:
09 2023
09 2023
Historique:
received:
24
10
2022
accepted:
28
02
2023
medline:
7
9
2023
pubmed:
15
4
2023
entrez:
14
4
2023
Statut:
ppublish
Résumé
Endometriosis is a common gynecological disorder characterized by the presence of the endometrial glands and the stroma outside the uterine cavity. The disease affects reproductive function and quality of life in women of reproductive age. Endometriosis is similar to tumors in some characteristics, such as glycolysis. PIM2 can promote the development of tumors, but the mechanism of PIM2 in endometriosis is still unclear. Therefore, our goal is to study the mechanism of PIM2 in endometriosis. Through immunohistochemistry, we found PIM2, HK2, PKM2, SMH (smooth muscle myosin heavy chain), Desmin, and α-SMA (α-smooth muscle actin) were strongly expressed in the ovarian endometriosis. In endometriotic cells, PIM2 enhanced glycolysis and fibrosis via upregulating the expression of PKM2. Moreover, the PIM2 inhibitor SMI-4a inhibited the development of endometriosis. And we established a PIM2 knockout mouse model of endometriosis to demonstrate the role of PIM2 in vivo. In summary, our study indicates that PIM2 promotes the development of endometriosis. PIM2 may serve as a promising therapeutic target for endometriosis.
Identifiants
pubmed: 37059967
doi: 10.1007/s43032-023-01208-w
pii: 10.1007/s43032-023-01208-w
doi:
Substances chimiques
PIM2 protein, human
0
Proto-Oncogene Proteins
0
Protein Serine-Threonine Kinases
EC 2.7.11.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2692-2702Informations de copyright
© 2023. The Author(s), under exclusive licence to Society for Reproductive Investigation.
Références
Burney RO, Giudice LC. Pathogenesis and pathophysiology of endometriosis. Fertil Steril. 2012;98(3):511–9.
doi: 10.1016/j.fertnstert.2012.06.029
pubmed: 22819144
Patzkowsky K. Rethinking endometriosis and pelvic pain. J Clin Invest. 2021;131(20):e154876.
Vercellini P, Vigano P, Somigliana E, Fedele L. Endometriosis: pathogenesis and treatment. Nat Rev Endocrinol. 2014;10(5):261–75.
doi: 10.1038/nrendo.2013.255
pubmed: 24366116
Laganà AS, Garzon S, Götte M, Viganò P, Franchi M, Ghezzi F, et al. The pathogenesis of endometriosis: molecular and cell biology insights. Int J Mol Sci. 2019;20(22):5615.
Taylor HS, Kotlyar AM, Flores VA. Endometriosis is a chronic systemic disease: clinical challenges and novel innovations. The Lancet. 2021;397(10276):839–52.
doi: 10.1016/S0140-6736(21)00389-5
Hang Y, Tan L, Chen Q, Liu Q, Jin Y. E3 ubiquitin ligase TRIM24 deficiency promotes NLRP3/caspase-1/IL-1beta-mediated pyroptosis in endometriosis. Cell Biol Int. 2021;45(7):1561–70.
doi: 10.1002/cbin.11592
pubmed: 33724611
Young VJ, Brown JK, Maybin J, Saunders PT, Duncan WC, Horne AW. Transforming growth factor-beta induced Warburg-like metabolic reprogramming may underpin the development of peritoneal endometriosis. J Clin Endocrinol Metab. 2014;99(9):3450–9.
doi: 10.1210/jc.2014-1026
pubmed: 24796928
pmcid: 4207934
Ganapathy-Kanniappan S, Geschwind JF. Tumor glycolysis as a target for cancer therapy: progress and prospects. Mol Cancer. 2013;12:152.
doi: 10.1186/1476-4598-12-152
pubmed: 24298908
pmcid: 4223729
Vander Heiden MG, Cantley LC, Thompson CB. Understanding the Warburg effect: the metabolic requirements of cell proliferation. Science. 2009;324(5930):1029–33.
doi: 10.1126/science.1160809
pubmed: 19460998
pmcid: 2849637
Mikawa T, Lleonart ME, Takaori-Kondo A, Inagaki N, Yokode M, Kondoh H. Dysregulated glycolysis as an oncogenic event. Cell Mol Life Sci. 2015;72(10):1881–92.
Kobayashi H, Shigetomi H, Imanaka S. Nonhormonal therapy for endometriosis based on energy metabolism regulation. Reprod Fertil. 2021;2(4):C42–57.
doi: 10.1530/RAF-21-0053
pubmed: 35118411
pmcid: 8788578
Ding H, Jiang L, Xu J, Bai F, Zhou Y, Yuan Q, et al. Inhibiting aerobic glycolysis suppresses renal interstitial fibroblast activation and renal fibrosis. Am J Physiol Renal Physiol. 2017;313(3):F561–75.
doi: 10.1152/ajprenal.00036.2017
pubmed: 28228400
Hu WP, Tay SK, Zhao Y. Endometriosis-specific genes identified by real-time reverse transcription-polymerase chain reaction expression profiling of endometriosis versus autologous uterine endometrium. J Clin Endocrinol Metab. 2006;91(1):228–38.
doi: 10.1210/jc.2004-1594
pubmed: 16249290
Blanco-Aparicio C, Carnero A. Pim kinases in cancer: diagnostic, prognostic and treatment opportunities. Biochem Pharmacol. 2013;85(5):629–43.
doi: 10.1016/j.bcp.2012.09.018
pubmed: 23041228
Yang T, Ren C, Qiao P, Han X, Wang L, Lv S, et al. PIM2-mediated phosphorylation of hexokinase 2 is critical for tumor growth and paclitaxel resistance in breast cancer. Oncogene. 2018;37(45):5997–6009.
doi: 10.1038/s41388-018-0386-x
pubmed: 29985480
pmcid: 6224402
Kronschnabl P, Grunweller A, Hartmann RK, Aigner A, Weirauch U. Inhibition of PIM2 in liver cancer decreases tumor cell proliferation in vitro and in vivo primarily through the modulation of cell cycle progression. Int J Oncol. 2020;56(2):448–59.
pubmed: 31894300
Tang X, Cao T, Zhu Y, Zhang L, Chen J, Liu T, et al. PIM2 promotes hepatocellular carcinoma tumorigenesis and progression through activating NF-kappaB signaling pathway. Cell Death Dis. 2020;11(7):510.
doi: 10.1038/s41419-020-2700-0
pubmed: 32641749
pmcid: 7343807
Wang F, Xu L, Dong G, Zhu M, Liu L, Wang B. PIM2 deletion alleviates lipopolysaccharide (LPS)-induced respiratory distress syndrome (ARDS) by suppressing NLRP3 inflammasome. Biochem Biophys Res Commun. 2020;533(4):1419–26.
doi: 10.1016/j.bbrc.2020.08.109
pubmed: 33333710
Wang L, Chen Y, Wu S, Wang L, Tan F, Li F. PIM2-mediated phosphorylation contributes to granulosa cell survival via resisting apoptosis during folliculogenesis. Clin Transl Med. 2021;11(3): e359.
doi: 10.1002/ctm2.359
pubmed: 33783992
pmcid: 7943893
Han X, Ren C, Yang T, Qiao P, Wang L, Jiang A, et al. Negative regulation of AMPKalpha1 by PIM2 promotes aerobic glycolysis and tumorigenesis in endometrial cancer. Oncogene. 2019;38(38):6537–49.
doi: 10.1038/s41388-019-0898-z
pubmed: 31358902
Yu Z, Zhao X, Huang L, Zhang T, Yang F, Xie L, et al. Proviral insertion in murine lymphomas 2 (PIM2) oncogene phosphorylates pyruvate kinase M2 (PKM2) and promotes glycolysis in cancer cells. J Biol Chem. 2013;288(49):35406–16.
doi: 10.1074/jbc.M113.508226
pubmed: 24142698
pmcid: 3853288
Zeitvogel A, Baumann R, Starzinski-Powitz A. Identification of an invasive, N-cadherin-expressing epithelial cell type in endometriosis using a new cell culture model. Am J Pathol. 2001;159(5):1839–52.
doi: 10.1016/S0002-9440(10)63030-1
pubmed: 11696444
pmcid: 1867070
Ding D, Liu X, Duan J, Guo SW. Platelets are an unindicted culprit in the development of endometriosis: clinical and experimental evidence. Hum Reprod. 2015;30(4):812–32.
doi: 10.1093/humrep/dev025
pubmed: 25740881
Lu C, Ren C, Yang T, Sun Y, Qiao P, Han X, et al. Fructose-1, 6-bisphosphatase 1 interacts with NF-kappaB p65 to regulate breast tumorigenesis via PIM2 induced phosphorylation. Theranostics. 2020;10(19):8606–18.
doi: 10.7150/thno.46861
pubmed: 32754266
pmcid: 7392005
Yang T, Ren C, Lu C, Qiao P, Han X, Wang L, et al. Phosphorylation of HSF1 by PIM2 induces PD-L1 expression and promotes tumor growth in breast cancer. Cancer Res. 2019;79(20):5233–44.
doi: 10.1158/0008-5472.CAN-19-0063
pubmed: 31409638
Yao Q, Jing G, Zhang X, Li M, Yao Q, Wang L. Cinnamic acid inhibits cell viability, invasion, and glycolysis in primary endometrial stromal cells by suppressing NF-kappaB-induced transcription of PKM2. Biosci Rep. 2021. https://doi.org/10.1042/BSR20211828 .
Mehedintu C, Plotogea MN, Ionescu S, Antonovici M. Endometriosis still a challenge. J Med Life. 2014;7(3):349–57.
pubmed: 25408753
pmcid: 4233437
Signorile PG, Baldi A. New evidence in endometriosis. Int J Biochem Cell Biol. 2015;60:19–22.
doi: 10.1016/j.biocel.2014.12.019
pubmed: 25578564
Zondervan KT, Becker CM, Koga K, Missmer SA, Taylor RN, Vigano P. Endometriosis Nat Rev Dis Primers. 2018;4(1):9.
doi: 10.1038/s41572-018-0008-5
pubmed: 30026507
Wang Y, Xiu J, Ren C, Yu Z. Protein kinase PIM2: a simple PIM family kinase with complex functions in cancer metabolism and therapeutics. J Cancer. 2021;12(9):2570–81.
doi: 10.7150/jca.53134
pubmed: 33854618
pmcid: 8040705
Warmoes MO, Locasale JW. Heterogeneity of glycolysis in cancers and therapeutic opportunities. Biochem Pharmacol. 2014;92(1):12–21.
doi: 10.1016/j.bcp.2014.07.019
pubmed: 25093285
pmcid: 4254151
Levine AJ, Puzio-Kuter AM. The control of the metabolic switch in cancers by oncogenes and tumor suppressor genes. Science. 2010;330(6009):1340–4.
doi: 10.1126/science.1193494
pubmed: 21127244
McDonald JE, Kessler MM, Gardner MW, Buros AF, Ntambi JA, Waheed S, et al. Assessment of total lesion glycolysis by (18)F FDG PET/CT significantly improves prognostic value of GEP and ISS in myeloma. Clin Cancer Res. 2017;23(8):1981–7.
doi: 10.1158/1078-0432.CCR-16-0235
pubmed: 27698001
Brandes RP, Rezende F. Glycolysis and inflammation: partners in crime! Circ Res. 2021;129(1):30–2.
doi: 10.1161/CIRCRESAHA.121.319447
pubmed: 34166079
Erlich JR, To EE, Luong R, Liong F, Liong S, Oseghale O, et al. Glycolysis and the pentose phosphate pathway promote LPS-induced NOX2 oxidase- and IFN-beta-dependent inflammation in macrophages. Antioxidants (Basel). 2022;11(8):1488.
Wang S, Yu H, Gao J, Chen J, He P, Zhong H, et al. PALMD regulates aortic valve calcification via altered glycolysis and NF-kappaB-mediated inflammation. J Biol Chem. 2022;298(5): 101887.
doi: 10.1016/j.jbc.2022.101887
pubmed: 35367413
pmcid: 9065630
Wong N, De Melo J, Tang D. PKM2, a central point of regulation in cancer metabolism. Int J Cell Biol. 2013;2013: 242513.
doi: 10.1155/2013/242513
pubmed: 23476652
pmcid: 3586519
Zhang Z, Deng X, Liu Y, Liu Y, Sun L, Chen F. PKM2, function and expression and regulation. Cell Biosci. 2019;9:52.
doi: 10.1186/s13578-019-0317-8
pubmed: 31391918
pmcid: 6595688
Zhang Q, Duan J, Olson M, Fazleabas A, Guo SW. Cellular changes consistent with epithelial-mesenchymal transition and fibroblast-to-myofibroblast transdifferentiation in the progression of experimental endometriosis in baboons. Reprod Sci. 2016;23(10):1409–21.
doi: 10.1177/1933719116641763
pubmed: 27076446
pmcid: 5933178
Ganieva U, Nakamura T, Osuka S, Bayasula, Nakanishi N, Kasahara Y, et al. Involvement of transcription factor 21 in the pathogenesis of fibrosis in endometriosis. Am J Pathol. 2020;190(1):145–57.
Vigano P, Candiani M, Monno A, Giacomini E, Vercellini P, Somigliana E. Time to redefine endometriosis including its pro-fibrotic nature. Hum Reprod. 2018;33(3):347–52.
doi: 10.1093/humrep/dex354
pubmed: 29206943
Zeng X, Yue Z, Gao Y, Jiang G, Zeng F, Shao Y, et al. NR4A1 is involved in fibrogenesis in ovarian endometriosis. Cell Physiol Biochem. 2018;46(3):1078–90.
doi: 10.1159/000488838
pubmed: 29669342
Direkze NC, Forbes SJ, Brittan M, Hunt T, Jeffery R, Preston SL, et al. Multiple organ engraftment by bone-marrow-derived myofibroblasts and fibroblasts in bone-marrow-transplanted mice. Stem Cells. 2003;21(5):514–20.
doi: 10.1634/stemcells.21-5-514
pubmed: 12968105
Higashiyama R, Nakao S, Shibusawa Y, Ishikawa O, Moro T, Mikami K, et al. Differential contribution of dermal resident and bone marrow-derived cells to collagen production during wound healing and fibrogenesis in mice. J Invest Dermatol. 2011;131(2):529–36.
doi: 10.1038/jid.2010.314
pubmed: 20962852
Stone RC, Pastar I, Ojeh N, Chen V, Liu S, Garzon KI, et al. Epithelial-mesenchymal transition in tissue repair and fibrosis. Cell Tissue Res. 2016;365(3):495–506.
doi: 10.1007/s00441-016-2464-0
pubmed: 27461257
pmcid: 5011038