ERRα contributes to HDAC6-induced chemoresistance of osteosarcoma cells.
Cisplatin
Doxorubicin
ERRα
HDAC6
Osteosarcoma
Journal
Cell biology and toxicology
ISSN: 1573-6822
Titre abrégé: Cell Biol Toxicol
Pays: Switzerland
ID NLM: 8506639
Informations de publication
Date de publication:
06 2023
06 2023
Historique:
received:
19
05
2021
accepted:
03
09
2021
medline:
8
8
2023
pubmed:
16
9
2021
entrez:
15
9
2021
Statut:
ppublish
Résumé
Chemotherapy resistance is an important problem for clinical therapy of osteosarcoma (OS). The potential effects of histone deacetylases (HDACs) on OS chemoresistance are studied. The expression of HDACs in OS cells resistance to doxorubicin (Dox) and cisplatin (CDDP) is checked. Among 11 members of HDACs, levels of HDAC6 are significantly upregulated in OS cells resistance to Dox and CDDP. Inhibition of HDAC6 via its specific inhibitor ACY1215 restores chemosensitivity of OS-resistant cells. Further, HDAC6 directly binds with estrogen-related receptors alpha (ERRα) to regulate its acetylation and protein stability. Inhibition of ERRα further strengthens ACY1215-increased chemosensitivity of OS-resistant cells. Mechanistically, K129 acetylation is the key residue for HDAC6-regulated protein levels of ERRα. Collectively, we find that ERRα contributes to HDAC6-induced chemoresistance of OS cells. Inhibition of HDAC6/ERRα axis might be a potential approach to overcome chemoresistance and improve therapy efficiency for OS treatment. 1. HDAC6 was significantly upregulated in Dox and CDDP resistant OS cells; 2. Inhibition of HDAC6 can restore chemosensitivity of OS cells; 3. HDAC6 binds with ERRα at K129 to decrease its acetylation and increase protein stability; 4. ERRα contributes to HDAC6-induced chemoresistance of OS cells.
Identifiants
pubmed: 34524571
doi: 10.1007/s10565-021-09651-8
pii: 10.1007/s10565-021-09651-8
doi:
Substances chimiques
Cisplatin
Q20Q21Q62J
Doxorubicin
80168379AG
HDAC6 protein, human
EC 3.5.1.98
Histone Deacetylase 6
EC 3.5.1.98
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
813-825Informations de copyright
© 2021. The Author(s), under exclusive licence to Springer Nature B.V.
Références
Audet-Walsh E, Papadopoli DJ, Gravel SP, Yee T, Bridon G, Caron M, Bourque G, Giguere V, St-Pierre J. The PGC-1alpha/ERRalpha axis represses one-carbon metabolism and promotes sensitivity to anti-folate therapy in breast cancer. Cell Rep. 2016;14:920–31.
doi: 10.1016/j.celrep.2015.12.086
pubmed: 26804918
Bian XH, Liang ZX, Feng A, Salgado E, Shim H. HDAC inhibitor suppresses proliferation and invasion of breast cancer cells through regulation of miR-200c targeting CRKL. Biochem Pharmacol. 2018;147:30–7.
doi: 10.1016/j.bcp.2017.11.008
pubmed: 29155146
Brindisi M, Fiorillo M, Frattaruolo L, Sotgia F, Lisanti MP, Cappello AR. Cholesterol and mevalonate: two metabolites involved in breast cancer progression and drug resistance through the ERRalpha pathway. Cells. 2020;9:1819.
Caron C, Boyault C, Khochbin S. Regulatory cross-talk between lysine acetylation and ubiquitination: role in the control of protein stability. Bioessays. 2005;27:408–15.
doi: 10.1002/bies.20210
pubmed: 15770681
Chen P, Wang HB, Duan ZJ, Zou JX, Chen HW, He W, Wang JJ. Estrogen-related receptor alpha confers methotrexate resistance via attenuation of reactive oxygen species production and P53 mediated apoptosis in osteosarcoma cells. Biomed Res Int. 2014;2014:616025.
Chen P, Wang H, Yang F, Chen H, He W, Wang J. Curcumin promotes osteosarcoma cell death by activating miR-125a/ERRalpha signal pathway. J Cell Biochem. 2017;118:74–81.
doi: 10.1002/jcb.25612
pubmed: 27231954
Chen Y, Zhang K, Li Y, Guo R, Zhang K, Zhong G, He Q. Oestrogen-related receptor alpha mediates chemotherapy resistance of osteosarcoma cells via regulation of ABCB1. J Cell Mol Med. 2019;23:2115–24.
doi: 10.1111/jcmm.14123
pubmed: 30609256
pmcid: 6378180
Collier CD, Getty PJ, Greenfield EM. Targeting the cancer epigenome with histone deacetylase inhibitors in osteosarcoma. Adv Exp Med Biol. 2020;1258:55–75.
doi: 10.1007/978-3-030-43085-6_4
pubmed: 32767234
Deblois G, Smith HW, Tam IS, Gravel SP, Caron M, Savage P, Labbe DP, Begin LR, Tremblay ML, Park M, et al. ERRalpha mediates metabolic adaptations driving lapatinib resistance in breast cancer. Nat Commun. 2016;7:12156.
doi: 10.1038/ncomms12156
pubmed: 27402251
pmcid: 4945959
Dufour CR, Wilson BJ, Huss JM, Kelly DP, Alaynick WA, Downes M, Evans RM, Blanchette M, Giguere V. Genome-wide orchestration of cardiac functions by the orphan nuclear receptors ERRalpha and gamma. Cell Metab. 2007;5:345–56.
doi: 10.1016/j.cmet.2007.03.007
pubmed: 17488637
Fradet A, Bouchet M, Delliaux C, Gervais M, Kan C, Benetollo C, Pantano F, Vargas G, Bouazza L, Croset M, et al. Estrogen related receptor alpha in castration-resistant prostate cancer cells promotes tumor progression in bone. Oncotarget. 2016;7:77071–86.
doi: 10.18632/oncotarget.12787
pubmed: 27776343
pmcid: 5363569
Hanusova V, Caltova K, Svobodova H, Ambroz M, Skarka A, Murinova N, Kralova V, Tomsik P, Skalova L. The effects of beta-caryophyllene oxide and trans-nerolidol on the efficacy of doxorubicin in breast cancer cells and breast tumor-bearing mice. Biomed Pharmacother. 2017;95:828–36.
doi: 10.1016/j.biopha.2017.09.008
pubmed: 28903178
Hattinger CM, Fanelli M, Tavanti E, Vella S, Riganti C, Picci P, Serra M. Doxorubicin-resistant osteosarcoma: novel therapeutic approaches in sight? Future Oncol. 2017;13:673–7.
doi: 10.2217/fon-2016-0519
pubmed: 28183198
Huang JH, Xu Y, Lin FY. The inhibition of microRNA-326 by SP1/HDAC1 contributes to proliferation and metastasis of osteosarcoma through promoting SMO expression. J Cell Mol Med. 2020;24:10876–88.
doi: 10.1111/jcmm.15716
pubmed: 32743904
pmcid: 7521251
Isakoff MS, Bielack SS, Meltzer P, Gorlick R. Osteosarcoma: current treatment and a collaborative pathway to success. J Clin Oncol. 2015;33:3029–35.
doi: 10.1200/JCO.2014.59.4895
pubmed: 26304877
pmcid: 4979196
Jarzabek K, Koda M, Kozlowski L, Sulkowski S, Kottler ML, Wolczynski S. The significance of the expression of ERR alpha as a potential biomarker in breast cancer. J Steroid Biochem. 2009;113:127–33.
doi: 10.1016/j.jsbmb.2008.12.005
Kiany S, Harrison D, Gordon N. The histone deacetylase inhibitor Entinostat/Syndax 275 in osteosarcoma. Adv Exp Med Biol. 2020;1257:75–83.
doi: 10.1007/978-3-030-43032-0_7
pubmed: 32483732
Kim M, Jung JY, Choi S, Lee H, Morales LD, Koh JT, Kim SH, Choi YD, Choi C, Slaga TJ, et al. GFRA1 promotes cisplatin-induced chemoresistance in osteosarcoma by inducing autophagy. Autophagy. 2017;13:149–68.
doi: 10.1080/15548627.2016.1239676
pubmed: 27754745
Lee SW, Yeon SK, Kim GW, Lee DH, Jeon YH, Yoo J, Kim SY, Kwon SH. HDAC6-selective inhibitor overcomes bortezomib resistance in multiple myeloma. Int J Mol Sci. 2021;22:1341.
Lilienthal I, Herold N. Targeting molecular mechanisms underlying treatment efficacy and resistance in osteosarcoma: a review of current and future strategies. Int J Mol Sci. 2020;21:6885.
Lin X, Chai G, Wu Y, Li J, Chen F, Liu J, Luo G, Tauler J, Du J, Lin S, et al. RNA m(6)A methylation regulates the epithelial mesenchymal transition of cancer cells and translation of Snail. Nat Commun. 2019;10:2065.
doi: 10.1038/s41467-019-09865-9
pubmed: 31061416
pmcid: 6502834
Luetke A, Meyers PA, Lewis I, Juergens H. Osteosarcoma treatment - where do we stand? A state of the art review. Cancer Treat Rev. 2014;40:523–32.
doi: 10.1016/j.ctrv.2013.11.006
pubmed: 24345772
Marks PA. The clinical development of histone deacetylase inhibitors as targeted anticancer drugs. Expert Opin Inv Drug. 2010;19:1049–66.
doi: 10.1517/13543784.2010.510514
Matsuyama A, Shimazu T, Sumida Y, Saito A, Yoshimatsu Y, Seigneurin-Berny D, Osada H, Komatsu Y, Nishino N, Khochbin S, et al. In vivo destabilization of dynamic microtubules by HDAC6-mediated deacetylation. EMBO J. 2002;21:6820–31.
doi: 10.1093/emboj/cdf682
pubmed: 12486003
pmcid: 139102
McGuire JJ, Nerlakanti N, Lo CH, Tauro M, Utset-Ward TJ, Reed DR, Lynch CC. Histone deacetylase inhibition prevents the growth of primary and metastatic osteosarcoma. Int J Cancer. 2020;147:2811–23.
doi: 10.1002/ijc.33046
pubmed: 32599665
pmcid: 7787271
Murahari S, Jalkanen AL, Kulp SK, Chen CS, Modiano JF, London CA, Kisseberth WC. Sensitivity of osteosarcoma cells to HDAC inhibitor AR-42 mediated apoptosis. BMC Cancer. 2017;17:67.
doi: 10.1186/s12885-017-3046-6
pubmed: 28109246
pmcid: 5251323
Nagy A, Munkacsy G, Gyorffy B. Pancancer survival analysis of cancer hallmark genes. Sci Rep. 2021;11:6047.
doi: 10.1038/s41598-021-84787-5
pubmed: 33723286
pmcid: 7961001
Pulya S, Amin SA, Adhikari N, Biswas S, Jha T, Ghosh B. HDAC6 as privileged target in drug discovery: a perspective. Pharmacol Res. 2021;163:105274.
Santo L, Hideshima T, Kung AL, Tseng JC, Tamang D, Yang M, Jarpe M, van Duzer JH, Mazitschek R, Ogier WC, et al. Preclinical activity, pharmacodynamic, and pharmacokinetic properties of a selective HDAC6 inhibitor, ACY-1215, in combination with bortezomib in multiple myeloma. Blood. 2012;119:2579–89.
doi: 10.1182/blood-2011-10-387365
pubmed: 22262760
pmcid: 3337713
Stein RA, McDonnell DP. Estrogen-related receptor alpha as a therapeutic target in cancer. Endocr Relat Cancer. 2006;13:S25–32.
doi: 10.1677/erc.1.01292
pubmed: 17259555
Suzuki T, Miki Y, Moriya T, Shimada N, Ishida T, Hirakawa H, Ohuchi N, Sasano H. Estrogen-related receptor alpha in human breast carcinoma as a potent prognostic factor. Cancer Res. 2004;64:4670–6.
doi: 10.1158/0008-5472.CAN-04-0250
pubmed: 15231680
Vernier M, Dufour CR, McGuirk S, Scholtes C, Li X, Bourmeau G, Kuasne H, Park M, St-Pierre J, Audet-Walsh E, Giguere V. Estrogen-related receptors are targetable ROS sensors. Genes Dev. 2020;34:544–59.
doi: 10.1101/gad.330746.119
pubmed: 32079653
pmcid: 7111261
Watanabe K, Okamoto K, Yonehara S. Sensitization of osteosarcoma cells to death receptor-mediated apoptosis by HDAC inhibitors through downregulation of cellular FLIP. Cell Death Differ. 2005;12:10–8.
doi: 10.1038/sj.cdd.4401507
pubmed: 15540114
Wilson BJ, Tremblay AM, Deblois G, Sylvain-Drolet G, Giguere V. An acetylation switch modulates the transcriptional activity of estrogen-related receptor alpha. Mol Endocrinol. 2010;24:1349–58.
doi: 10.1210/me.2009-0441
pubmed: 20484414
pmcid: 5417470
Wu F, Wang J, Wang Y, Kwok TT, Kong SK, Wong C. Estrogen-related receptor alpha (ERRalpha) inverse agonist XCT-790 induces cell death in chemotherapeutic resistant cancer cells. Chem Biol Interact. 2009;181:236–42.
doi: 10.1016/j.cbi.2009.05.008
pubmed: 19464277
Yang WB, Hsu CC, Hsu TI, Liou JP, Chang KY, Chen PY, Liu JJ, Yang ST, Wang JY, Yeh SH, et al. Increased activation of HDAC1/2/6 and Sp1 underlies therapeutic resistance and tumor growth in glioblastoma. Neuro Oncol. 2020;22:1439–51.
doi: 10.1093/neuonc/noaa103
pubmed: 32328646
pmcid: 7566541
Zhang M, Xiang S, Joo HY, Wang L, Williams KA, Liu W, Hu C, Tong D, Haakenson J, Wang C, et al. HDAC6 deacetylates and ubiquitinates MSH2 to maintain proper levels of MutSalpha. Mol Cell. 2014;55:31–46.
doi: 10.1016/j.molcel.2014.04.028
pubmed: 24882211
pmcid: 4188514