Downregulation of DKK-1 and Upregulation of β-Catenin in Cancer Floating Spheroids is Associated with Chemoresistance to Wnt Signaling Pathway Inhibitors
Yıl: 2022 Cilt: 6 Sayı: 3 Sayfa Aralığı: 241 - 246 Metin Dili: İngilizce DOI: 10.14744/ejmo.2022.50709 İndeks Tarihi: 03-11-2022
Downregulation of DKK-1 and Upregulation of β-Catenin in Cancer Floating Spheroids is Associated with Chemoresistance to Wnt Signaling Pathway Inhibitors
Öz: Objectives: DKK-1, a negative regulator of β-catenin in the Wnt pathway is commonly upregulated in cancer cells but its expression and association to chemoresistance have not been investigated extensively. Our aim was to evaluate the expression of DKK-1 and β-catenin as well as the effect of the Wnt pathway modulators iCRT-14 (iCRT) and WAY626611 (WAY) alone or in combination with Nigericin (NIG) on the viability of cancer cells grown under routine conditions (RC) or as floating spheroids (FSs). Methods: RC or FSs from human prostate (PC3 and LnCAP) and breast (MCF-7 and MDA-MB231) cells were treated for 72 hs with WAY or iCRT. Cell viability was determined by the MTT or the CCK-8 assays and protein expression was determined by western blot analysis. Results: DKK-1 was expressed at different basal levels in RC but was undetectable in FSs. β-catenin expression was in- creased in FSs. RC of PC3 and MCF-7 were sensitive to both iCRT and WAY but FSs generated from these cell lines were resistant to both drugs. NIG potentiated the effect of both Wnt inhibitors in FSs. Conclusion: Marked changes in the expression of Wnt pathway proteins, DKK-1 and β-catenin in FSs are associated with resistance to WAY and iCRT.
Anahtar Kelime: Belge Türü: Makale Makale Türü: Araştırma Makalesi Erişim Türü: Erişime Açık
- 1. Rachner TD, Thiele S, Gobel A, Browne A, Fuessel S, Erdmann K, et al. High serum levels of Dickkopf-1 are associated with a poor prognosis in prostate cancer patients. BMC Cancer 2014;14:649. [CrossRef ]
- 2. Zhou SJ, Zhuo SR, Yang XQ, Qin CX, Wang ZL. Serum Dick - kopf-1 expression level positively correlates with a poor prog- nosis in breast cancer. Diagn Pathol 2014;9:161 [CrossRef ]
- 3. Sun DK, Wang L, Wang JM, Zhang P. Serum Dickkopf-1 levels as a clinical and prognostic factor in patients with bladder cancer. Genet Mol Res 2015;14:18181–7. [CrossRef ]
- 4. Li J, Gong W, Li X, Wan R, Mo F, Zhang Z, et al. Recent progress of Wnt Pathway Inhibitor Dickkopf-1 in liver cancer. J Nanosci Nanotechnol 2018;18:5192–206. [CrossRef ]
- 5. Thudi NK, Martin CK, Murahari S, Shu ST, Lanigan LG, Wer- beck JL, et al. Dickkopf-1 (DKK-1) stimulated prostate cancer growth and metastasis and inhibited bone formation in os- teoblastic bone metastases. Prostate 2011;71:615–25. [CrossRef ]
- 6. D'Amelio P, Roato I, Oderda M, Soria F, Zitella A, Ferracini R, et al. DKK-1 in prostate cancer diagnosis and follow up. BMC Clin Pathol 2014;14:11. [CrossRef ]
- 7. Hall CL, Daignault SD, Shah RB, Pienta KJ, Keller ET. Dickkopf-1 expression increases early in prostate cancer development and decreases during progression from primary tumor to me- tastasis. Prostate. 2008;68:1396–404. [CrossRef ]
- 8. Kaushik V, Yakisich JS, Way LF, Azad N, Iyer AKV. Chemoresis- tance of cancer floating cells is independent of their ability to form 3D structures: Implications for anticancer drug screen- ing. J Cell Physiol 2019;234:4445–53. [CrossRef ]
- 9. Pelletier JC, Lundquist JT 4th, Gilbert AM, Alon N, Bex FJ, Bhat BM, et al. (1-(4-(Naphthalen-2-yl)pyrimidin-2-yl)piperidin-4-yl) methanamine: a wingless beta-catenin agonist that increases bone formation rate. J Med Chem 2009;52:6962–5. [CrossRef ]
- 10. Bilir B, Kucuk O, Moreno CS. Wnt signaling blockage inhibits cell proliferation and migration, and induces apoptosis in tri- ple-negative breast cancer cells. J Transl Med 2013;11:280.
- 11. Yakisich JS, Azad N, Kaushik V, O'Doherty GA, Iyer AK. Nigeri- cin decreases the viability of multidrug-resistant cancer cells and lung tumorspheres and potentiates the effects of cardiac glycosides. Tumour Biol 2017;39:1010428317694310. [CrossRef ]
- 12. Liu F, Li W, Hua S, Han Y, Xu Z, Wan D, et al. Nigericin exerts anticancer effects on human colorectal cancer cells by in- hibiting Wnt/β-catenin signaling pathway. Mol Cancer Ther 2018;17:952–65. [CrossRef ]
- 13. Ye J, Xin L, Liu J, Tang T, Bao X, Yan Y. Dkk1 inhibits malignant transformation induced by Bmi1 via the β-catenin signaling axis in WB-F344 oval cells. FEBS Open Bio 2021;11:1854–66.
- 14. Enochson L, Stenberg J, Brittberg M, Lindahl A. GDF5 reduces MMP13 expression in human chondrocytes via DKK1 mediat- ed canonical Wnt signaling inhibition. Osteoarthritis Cartilage 2014;22:566–77. [CrossRef ]
- 15. Gonsalves FC, Klein K, Carson BB, Katz S, Ekas LA, Evans S, et al. An RNAi-based chemical genetic screen identifies three small-molecule inhibitors of the Wnt/wingless signaling path- way. Proc Natl Acad Sci U S A 2011;108:5954–63. [CrossRef ]
- 16. Li L, Liu HC, Wang C, Liu X, Hu FC, Xie N, et al. Overexpression of β-Catenin induces cisplatin resistance in oral squamous cell carcinoma. Biomed Res Int 2016;2016:5378567. [CrossRef ]
- 17. Yu G, Wu F, Wang E. KLF8 Promotes temozolomide resistance in glioma cells via β-Catenin activation. Cell Physiol Biochem 2016;38:1596–604. [CrossRef ]
- 18. Xu Z, Shen J, Hua S, Wan D, Chen Q, Han Y, et al. High-through- put sequencing of circRNAs reveals novel insights into mech- anisms of nigericin in pancreatic cancer. BMC Genomics 2019;20:716. [CrossRef ]
- 19. He J, Xie Q, Xu H, Li J, Li Y. Circular RNAs and cancer. Cancer Lett 2017;396:138–44. [CrossRef ]
- 20. Li YF, Zhang J, Yu L. Circular RNAs regulate cancer onset and progression via Wnt/β-Catenin signaling pathway. Yonsei Med J 2019;60:1117–28. [CrossRef ]
- 21. Yakisich JS, Venkatadri R, Azad N, Iyer AKV. Chemoresistance of lung and breast cancer cells growing under prolonged pe- riods of serum starvation. J Cell Physiol 2017;232:2033–43.
| APA | Kaushik V, Yakisich J, Kulkarni Y, azad n, Iyer A (2022). Downregulation of DKK-1 and Upregulation of β-Catenin in Cancer Floating Spheroids is Associated with Chemoresistance to Wnt Signaling Pathway Inhibitors. , 241 - 246. 10.14744/ejmo.2022.50709 |
| Chicago | Kaushik Vivek,Yakisich Juan,Kulkarni Yogesh,azad neelam,Iyer Anand Krishnan V. Downregulation of DKK-1 and Upregulation of β-Catenin in Cancer Floating Spheroids is Associated with Chemoresistance to Wnt Signaling Pathway Inhibitors. (2022): 241 - 246. 10.14744/ejmo.2022.50709 |
| MLA | Kaushik Vivek,Yakisich Juan,Kulkarni Yogesh,azad neelam,Iyer Anand Krishnan V. Downregulation of DKK-1 and Upregulation of β-Catenin in Cancer Floating Spheroids is Associated with Chemoresistance to Wnt Signaling Pathway Inhibitors. , 2022, ss.241 - 246. 10.14744/ejmo.2022.50709 |
| AMA | Kaushik V,Yakisich J,Kulkarni Y,azad n,Iyer A Downregulation of DKK-1 and Upregulation of β-Catenin in Cancer Floating Spheroids is Associated with Chemoresistance to Wnt Signaling Pathway Inhibitors. . 2022; 241 - 246. 10.14744/ejmo.2022.50709 |
| Vancouver | Kaushik V,Yakisich J,Kulkarni Y,azad n,Iyer A Downregulation of DKK-1 and Upregulation of β-Catenin in Cancer Floating Spheroids is Associated with Chemoresistance to Wnt Signaling Pathway Inhibitors. . 2022; 241 - 246. 10.14744/ejmo.2022.50709 |
| IEEE | Kaushik V,Yakisich J,Kulkarni Y,azad n,Iyer A "Downregulation of DKK-1 and Upregulation of β-Catenin in Cancer Floating Spheroids is Associated with Chemoresistance to Wnt Signaling Pathway Inhibitors." , ss.241 - 246, 2022. 10.14744/ejmo.2022.50709 |
| ISNAD | Kaushik, Vivek vd. "Downregulation of DKK-1 and Upregulation of β-Catenin in Cancer Floating Spheroids is Associated with Chemoresistance to Wnt Signaling Pathway Inhibitors". (2022), 241-246. https://doi.org/10.14744/ejmo.2022.50709 |
| APA | Kaushik V, Yakisich J, Kulkarni Y, azad n, Iyer A (2022). Downregulation of DKK-1 and Upregulation of β-Catenin in Cancer Floating Spheroids is Associated with Chemoresistance to Wnt Signaling Pathway Inhibitors. Eurasian Journal of Medicine and Oncology, 6(3), 241 - 246. 10.14744/ejmo.2022.50709 |
| Chicago | Kaushik Vivek,Yakisich Juan,Kulkarni Yogesh,azad neelam,Iyer Anand Krishnan V. Downregulation of DKK-1 and Upregulation of β-Catenin in Cancer Floating Spheroids is Associated with Chemoresistance to Wnt Signaling Pathway Inhibitors. Eurasian Journal of Medicine and Oncology 6, no.3 (2022): 241 - 246. 10.14744/ejmo.2022.50709 |
| MLA | Kaushik Vivek,Yakisich Juan,Kulkarni Yogesh,azad neelam,Iyer Anand Krishnan V. Downregulation of DKK-1 and Upregulation of β-Catenin in Cancer Floating Spheroids is Associated with Chemoresistance to Wnt Signaling Pathway Inhibitors. Eurasian Journal of Medicine and Oncology, vol.6, no.3, 2022, ss.241 - 246. 10.14744/ejmo.2022.50709 |
| AMA | Kaushik V,Yakisich J,Kulkarni Y,azad n,Iyer A Downregulation of DKK-1 and Upregulation of β-Catenin in Cancer Floating Spheroids is Associated with Chemoresistance to Wnt Signaling Pathway Inhibitors. Eurasian Journal of Medicine and Oncology. 2022; 6(3): 241 - 246. 10.14744/ejmo.2022.50709 |
| Vancouver | Kaushik V,Yakisich J,Kulkarni Y,azad n,Iyer A Downregulation of DKK-1 and Upregulation of β-Catenin in Cancer Floating Spheroids is Associated with Chemoresistance to Wnt Signaling Pathway Inhibitors. Eurasian Journal of Medicine and Oncology. 2022; 6(3): 241 - 246. 10.14744/ejmo.2022.50709 |
| IEEE | Kaushik V,Yakisich J,Kulkarni Y,azad n,Iyer A "Downregulation of DKK-1 and Upregulation of β-Catenin in Cancer Floating Spheroids is Associated with Chemoresistance to Wnt Signaling Pathway Inhibitors." Eurasian Journal of Medicine and Oncology, 6, ss.241 - 246, 2022. 10.14744/ejmo.2022.50709 |
| ISNAD | Kaushik, Vivek vd. "Downregulation of DKK-1 and Upregulation of β-Catenin in Cancer Floating Spheroids is Associated with Chemoresistance to Wnt Signaling Pathway Inhibitors". Eurasian Journal of Medicine and Oncology 6/3 (2022), 241-246. https://doi.org/10.14744/ejmo.2022.50709 |
