Open Access

Downregulation of complement factor H attenuates the stemness of MDA‑MB‑231 breast cancer cells via modulation of the ERK and p38 signaling pathways

  • Authors:
    • Soon Yong Park
    • Da-Young Eum
    • Yunho Jin
    • Chae Young Lee
    • Jae Woong Shim
    • Si Ho Choi
    • Seong-Joon Park
    • Kyu Heo
    • Yoo Jin Choi
  • View Affiliations

  • Published online on: October 18, 2023     https://doi.org/10.3892/ol.2023.14107
  • Article Number: 521
  • Copyright: © Park et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The complement system is a powerful innate immune system deployed in the immediate response to pathogens and cancer cells. Complement factor H (CFH), one of the regulators involved in the complement cascade, can interrupt the death of target cells. Certain types of cancer, such as breast cancer, can adopt an aggressive phenotype, such as breast cancer stem cells (BCSCs), through enhancement of the defense system against complement attack by amplifying various complement regulators. However, little is known about the association between CFH and BCSCs. In the present study, the roles of CFH in the CSC characteristics and radioresistance of MDA‑MB‑231 human breast cancer cells were investigated. CFH knockdown in MDA‑MB‑231 cells decreased the viability of the cells upon complement cascade activation. Notably, CFH knockdown also decreased cell survival and suppressed mammosphere formation, cell migration and cell invasion by attenuating radioresistance. Additionally, CFH knockdown further enhanced irradiation‑induced apoptosis through G2/M cell cycle arrest. It was also discovered that CFH knockdown attenuated the aggressive phenotypes of cancer cells by regulating CSC‑associated gene expression. Finally, by microarray analysis, it was found that the expression of erythrocyte membrane protein band 4.1‑like 3 (EPB41L3) was markedly increased following CFH knockdown. EPB41L3 inhibited ERK and activated the p38 MAPK signaling pathway. Taken together, these results indicated that CFH knockdown attenuated CSC properties and radioresistance in human breast cancer cells via controlling MAPK signaling and through upregulation of the tumor suppressor, EPB41L3.
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December-2023
Volume 26 Issue 6

Print ISSN: 1792-1074
Online ISSN:1792-1082

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Spandidos Publications style
Park SY, Eum D, Jin Y, Lee CY, Shim JW, Choi SH, Park S, Heo K and Choi YJ: Downregulation of complement factor H attenuates the stemness of MDA‑MB‑231 breast cancer cells via modulation of the ERK and p38 signaling pathways. Oncol Lett 26: 521, 2023
APA
Park, S.Y., Eum, D., Jin, Y., Lee, C.Y., Shim, J.W., Choi, S.H. ... Choi, Y.J. (2023). Downregulation of complement factor H attenuates the stemness of MDA‑MB‑231 breast cancer cells via modulation of the ERK and p38 signaling pathways. Oncology Letters, 26, 521. https://doi.org/10.3892/ol.2023.14107
MLA
Park, S. Y., Eum, D., Jin, Y., Lee, C. Y., Shim, J. W., Choi, S. H., Park, S., Heo, K., Choi, Y. J."Downregulation of complement factor H attenuates the stemness of MDA‑MB‑231 breast cancer cells via modulation of the ERK and p38 signaling pathways". Oncology Letters 26.6 (2023): 521.
Chicago
Park, S. Y., Eum, D., Jin, Y., Lee, C. Y., Shim, J. W., Choi, S. H., Park, S., Heo, K., Choi, Y. J."Downregulation of complement factor H attenuates the stemness of MDA‑MB‑231 breast cancer cells via modulation of the ERK and p38 signaling pathways". Oncology Letters 26, no. 6 (2023): 521. https://doi.org/10.3892/ol.2023.14107