The Characterization of Acute Myeloblastic Leukemia-M2 Cell Lines with Suppressed Stromal Interaction Molecule 1 (STIM1) and its Impact on Calcium/Reactive Oxygen Species Profiles
Eman Salem Algariri 1,2, Rabiatul Basria S. M. N. Mydin 1*, Emmanuel Jairaj Moses 1, Nur Arzuar Abdul Rahim 3, Narazah Mohd Yusoff 3
Journal of Angiotherapy 8(1) 1-10 https://doi.org/10.25163/angiotherapy.819435
Submitted: 28 November 2023 Revised: 18 January 2024 Published: 24 January 2024
Abstract
Introduction: Acute myeloid leukemia-M2 subtype (AML-M2) is a severe type of blood cancer that has a high rate of recurrence and death. Recent cancer research has linked stromal interaction molecule 1 (STIM1) and calcium/reactive oxygen species (ROS) interactions to cancer progression, drug resistance, and cancer cell self-renewal. However, the involvement of STIM1 in the modulation of calcium and ROS activities and AML-M2 cell survival is still unclear. Methods: The current study uses dicer-substrate siRNA (dsiRNA) knockdown of STIM1 to assess its functional activity in the AML-M2 cell line. Following STIM1 knockdown, the expression levels of genes involved in cell survival and ROS generation were measured by RT-qPCR. Calcium influx, ROS generation, cell proliferation, and colony formation were all evaluated. Results: Knocking down STIM1 exhibited a reduction in calcium influx and ROS generation. Kasumi-1 cell proliferation and colony formation were inhibited following STIM1 knockdown. Further transcriptomic profiling in this knockdown model revealed downregulation of KRAS, MAPK, C-MYC, Akt, NOX2, and PKC. Conclusion: The findings point to STIM1's potential role in promoting AML-M2 cell survival through calcium/ROS interplay-mediated control of KRAS and Akt-related pathways. Furthermore, it might recommend STIM1 and/or ROS for targeted therapy, which may contribute to regression of disease and improve the AML therapeutic strategy.
Keywords: Kasumi-1, STIM1, Acute Myeloblastic Leukemia-M2, cancer, disease
References
Chen YF, Lin PC, Yeh YM, Chen LH, Shen MR (2019) Store-operated Ca2+ entry in tumor progression: from molecular mechanisms to clinical implications. Cancers 11(7):899. https://doi.org/10.3390/cancers11070899
https://doi.org/10.3390/cancers11070899
Cheng H, Wang S, Feng R (2016) STIM1 plays an important role in TGF-β-induced suppression of breast cancer cell proliferation. Oncotarget 7(13):16866. doi: 10.18632/oncotarget.7619
https://doi.org/10.18632/oncotarget.7619
Debant M, Burgos M, Hemon P, Buscaglia P, Fali T, Melayah S, et al (2019) STIM1 at the plasma membrane as a new target in progressive chronic lymphocytic leukemia. Journal for immunotherapy of cancer 7, pp.1-13.
https://doi.org/10.1186/s40425-019-0591-3
Delierneux C, Kouba S, Shanmughapriya S, Potier-Cartereau M, Trebak M, Hempel N (2020) Mitochondrial calcium regulation of redox signaling in cancer. Cells 9(2), p.432.
https://doi.org/10.3390/cells9020432
Eun HS, Cho SY, Joo JS, Kang SH, Moon HS, Lee ES, et al (2017) Gene expression of NOX family members and their clinical significance in hepatocellular carcinoma. Scientific Reports 7(1):1-10. https://doi.org/10.1038/s41598-017-11280-3
https://doi.org/10.1038/s41598-017-11280-3
Feno S, Butera G, Vecellio Reane D, Rizzuto R, Raffaello A (2019) Crosstalk between calcium and ROS in pathophysiological conditions. Oxidative medicine and cellular longevity. https://doi.org/10.1155/2019/9324018
https://doi.org/10.1155/2019/9324018
Feno S, Butera G, Vecellio Reane D, Rizzuto R, Raffaello A (2019) Crosstalk between calcium and ROS in pathophysiological conditions. Oxidative medicine and cellular longevity 2019, pp.1-18.
https://doi.org/10.1155/2019/9324018
Fontayne A, Dang PM, Gougerot-Pocidalo MA, El Benna J (2002) Phosphorylation of p47 p hox Sites by PKC α, βΙΙ, δ, and ζ: Effect on Binding to p22 p hox and on NADPH Oxidase Activation. Biochemistry 41(24):7743-50. https://doi.org/10.1021/bi011953s
https://doi.org/10.1021/bi011953s
Ge C, Zeng B, Li R, Li Z, Fu Q, Wang W, et al (2019) Knockdown of STIM1 expression inhibits non-small-cell lung cancer cell proliferation in vitro and in nude mouse xenografts. Bioengineered 10(1):425-36. https://doi.org/10.1080/21655979.2019.1669518
https://doi.org/10.1080/21655979.2019.1669518
Görlach A, Bertram K, Hudecova S, Krizanova O (2015) Calcium and ROS: A mutual interplay. Redox biology 6:260-71. https://doi.org/10.1016/j.redox.2015.08.010
https://doi.org/10.1016/j.redox.2015.08.010
Grauers Wiktorin H, Aydin E, Hellstrand K, Martner A (2020) NOX2-derived reactive oxygen species in cancer. Oxidative Medicine and Cellular Longevity. https://doi.org/10.1155/2020/7095902
https://doi.org/10.1155/2020/7095902
Hempel N, Trebak M (2017) Crosstalk between calcium and reactive oxygen species signaling in cancer. Cell calcium 63:70-96. https://doi.org/10.1016/j.ceca.2017.01.007
https://doi.org/10.1016/j.ceca.2017.01.007
Kumari S, Badana AK, Malla R (2018) Reactive oxygen species: a key constituent in cancer survival. Biomarker insights 13:1177271918755391. https://doi.org/10.1177/1177271918755391
https://doi.org/10.1177/1177271918755391
Li W, Zhang M, Xu L, Lin D, Cai S, Zou F (2013) The apoptosis of non-small cell lung cancer induced by cisplatin through modulation of STIM1. Experimental and toxicologic pathology 65(7-8):1073-81. https://doi.org/10.1016/j.etp.2013.04.003
https://doi.org/10.1016/j.etp.2013.04.003
Liu H, Hughes JD, Rollins S, Chen B, Perkins E (2011) Calcium entry via ORAI1 regulates glioblastoma cell proliferation and apoptosis. Experimental and molecular pathology 91(3):753-60. https://doi.org/10.1016/j.yexmp.2011.09.005
https://doi.org/10.1016/j.yexmp.2011.09.005
Liu L, Wu N, Wang Y, Zhang X, Xia B, Tang J, et al (2019) TRPM7 promotes the epithelial-mesenchymal transition in ovarian cancer through the calcium-related PI3K/AKT oncogenic signaling. Journal of Experimental & Clinical Cancer Research 38(1):1-5. https://doi.org/10.1186/s13046-019-1061-y
https://doi.org/10.1186/s13046-019-1061-y
Liu Y, Jin M, Wang Y, Zhu J, Tan R, Zhao J, et al (2020) MCU-induced mitochondrial calcium uptake promotes mitochondrial biogenesis and colorectal cancer growth. Signal transduction and targeted therapy 5(1):1-3. https://doi.org/10.1038/s41392-020-0155-5
https://doi.org/10.1038/s41392-020-0155-5
Lunz V, Romanin C, Frischauf I (2019) STIM1 activation of Orai1. Cell calcium 77:29-38. https://doi.org/10.1016/j.ceca.2018.11.009
https://doi.org/10.1016/j.ceca.2018.11.009
Moloney JN, Stanicka J, Cotter TG (2017) Subcellular localization of the FLT3-ITD oncogene plays a significant role in the production of NOX-and p22phox-derived reactive oxygen species in acute myeloid leukemia. Leukemia research 52:34-42. https://doi.org/10.1016/j.leukres.2016.11.006
https://doi.org/10.1016/j.leukres.2016.11.006
National cancer institute SEER. Cancer stat facts: leukemia- acute myeloid leukemia (AML). 2021. https://seer.cancer.gov/statfacts/html/amyl.html. Accessed 20 June 2021.
Parascandolo A, Laukkanen MO (2019) Carcinogenesis and reactive oxygen species signaling: Interaction of the NADPH oxidase NOX1-5 and superoxide dismutase 1-3 signal transduction pathways. Antioxidants & Redox Signaling 30(3):443-86. https://doi.org/10.1089/ars.2017.7268
https://doi.org/10.1089/ars.2017.7268
Perillo B, Di Donato M, Pezone A, Di Zazzo E, Giovannelli P, Galasso G, et al (2020) ROS in cancer therapy: The bright side of the moon. Experimental & Molecular Medicine 52(2):192-203. https://doi.org/10.1038/s12276-020-0384-2
https://doi.org/10.1038/s12276-020-0384-2
Prasad S, Gupta SC, Tyagi AK (2017) Reactive oxygen species (ROS) and cancer: Role of antioxidative nutraceuticals. Cancer letters 387:95-105. https://doi.org/10.1016/j.canlet.2016.03.042
https://doi.org/10.1016/j.canlet.2016.03.042
Puccini M, Pilerci S, Merlini M, Grieco P, Scappini B, Bencini S, et al (2021) Venetoclax-Based Regimens for Relapsed/Refractory Acute Myeloid Leukemia in a Real-Life Setting: A Retrospective Single-Center Experience. Journal of Clinical Medicine 10(8), 1684.
https://doi.org/10.3390/jcm10081684
Reczek CR, Chandel NS (2018) ROS promotes cancer cell survival through calcium signaling. Cancer cell 33(6):949-51. https://doi.org/10.1016/j.ccell.2018.05.010
https://doi.org/10.1016/j.ccell.2018.05.010
Saint Fleur-Lominy S, Maus M, Vaeth M, Lange I, Zee I, Suh D, et al (2018) STIM1 and STIM2 mediate cancer-induced inflammation in T cell acute lymphoblastic leukemia. Cell reports 24(11):3045-60. https://doi.org/10.1016/j.celrep.2018.08.030
https://doi.org/10.1016/j.celrep.2018.08.030
Sasaki K, Ravandi F, Kadia TM, DiNardo CD, Short NJ, Borthakur G, et al (2021) De novo acute myeloid leukemia: A population-based study of outcome in the United States based on the Surveillance, Epidemiology, and End Results (SEER) database, 1980 to 2017. Cancer 127(12):2049-61. https://doi.org/10.1002/cncr.33458
https://doi.org/10.1002/cncr.33458
Sillar JR, Germon ZP, De Iuliis GN (2019) The role of reactive oxygen species in acute myeloid leukaemia. Int J Mol Sci 2019;20:6003.
https://doi.org/10.3390/ijms20236003
Sillar JR, Germon ZP, De Iuliis GN, Dun MD (2019) The role of reactive oxygen species in acute myeloid leukaemia. International journal of molecular sciences 20(23):6003. https://doi.org/10.3390/ijms20236003
https://doi.org/10.3390/ijms20236003
Terrié E, Déliot N, Benzidane Y, Harnois T, Cousin L, Bois P, et al (2021) Store-operated calcium channels control proliferation and self-renewal of cancer stem cells from glioblastoma. Cancers 13(14):3428. https://doi.org/10.3390/cancers13143428
https://doi.org/10.3390/cancers13143428
Thol F, Ganser A (2020) Treatment of relapsed acute myeloid leukemia. Current Treatment Options in Oncology 21(8):1-1. https://doi.org/10.1007/s11864-020-00765-5
https://doi.org/10.1007/s11864-020-00765-5
Umemura M, Baljinnyam E, Feske S, De Lorenzo MS, Xie LH, Feng X, et al (2014) Store-operated Ca2+ entry (SOCE) regulates melanoma proliferation and cell migration. PloS one 9(2):e89292. https://doi.org/10.1371/journal.pone.0089292
https://doi.org/10.1371/journal.pone.0089292
Vashisht A, Trebak M, Motiani RK (2015) STIM and Orai proteins as novel targets for cancer therapy. A Review in the Theme: Cell and Molecular Processes in Cancer Metastasis. American Journal of Physiology-Cell Physiology 309(7):C457-69. https://doi.org/10.1152/ajpcell.00064.2015
https://doi.org/10.1152/ajpcell.00064.2015
Wang SF, Chang YL, Tzeng YD, Wu CL, Wang YZ, Tseng LM, et al (2021) Mitochondrial stress adaptation promotes resistance to aromatase inhibitor in human breast cancer cells via ROS/calcium up-regulated amphiregulin-estrogen receptor loop signaling. Cancer Letters 523:82-99. https://doi.org/10.1016/j.canlet.2021.09.043
https://doi.org/10.1016/j.canlet.2021.09.043
Wang W, Ren Y, Wang L, Zhao W, Dong X, Pan J, et al (2018) Orai1 and Stim1 mediate the majority of store-operated calcium entry in multiple myeloma and have strong implications for adverse prognosis. Cellular Physiology and Biochemistry 48(6):2273-85. https://doi.org/10.1159/000492645
https://doi.org/10.1159/000492645
Wei S, Wang Y, Chai Q, Fang Q, Zhang Y, Wang J (2014) Potential crosstalk of Ca2+-ROS-dependent mechanism involved in apoptosis of Kasumi-1 cells mediated by heme oxygenase-1 small interfering RNA. International journal of oncology 45(6):2373-84. https://doi.org/10.3892/ijo.2014.2661
https://doi.org/10.3892/ijo.2014.2661
Wu M, Li C, Zhu X (2018) FLT3 inhibitors in acute myeloid leukemia. Journal of hematology & oncology 11(1), 1-11.
https://doi.org/10.1186/s13045-018-0675-4
Yang Y, Jiang Z, Wang B, Chang L, Liu J, Zhang L, et al (2017) Expression of STIM1 is associated with tumor aggressiveness and poor prognosis in breast cancer. Pathology-Research and Practice 213(9):1043-7. https://doi.org/10.1016/j.prp.2017.08.006
https://doi.org/10.1016/j.prp.2017.08.006
Zhao H, Yan G, Zheng L, Zhou Y, Sheng H, Wu L, et al (2020) STIM1 is a metabolic checkpoint regulating the invasion and metastasis of hepatocellular carcinoma. Theranostics 10(14):6483. doi:10.7150/thno.44025
https://doi.org/10.7150/thno.44025
Zheng S, Leclerc GM, Li B, Swords RT, Barredo JC (2018) Inhibition of the NEDD8 conjugation pathway induces calcium-dependent compensatory activation of the pro-survival MEK/ERK pathway in acute lymphoblastic leukemia. Oncotarget 9(5):5529. doi: 10.18632/oncotarget.23797
https://doi.org/10.18632/oncotarget.23797
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