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

被引:2
作者
Park, Soon Yong [1 ]
Eum, Da-Young [1 ]
Jin, Yunho [1 ]
Lee, Chae Young [1 ]
Shim, Jae Woong [1 ]
Choi, Si Ho [1 ]
Park, Seong-Joon [1 ]
Heo, Kyu [1 ]
Choi, Yoo Jin [1 ]
机构
[1] Dongnam Inst Radiol & Med Sci, Res Dept Oncol, 40 Jwadong Gil, Busan 460333, South Korea
关键词
CFH; radioresistance; cancer stemness; TNBC; MAPK pathway; ACTIVATION; CXCR4; PROGRESSION; METASTASIS; EXPRESSION; PROTEINS;
D O I
10.3892/ol.2023.14107
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
引用
收藏
页数:12
相关论文
共 49 条
  • [1] The role of the complement system in cancer
    Afshar-Kharghan, Vahid
    [J]. JOURNAL OF CLINICAL INVESTIGATION, 2017, 127 (03) : 780 - 789
  • [2] Down-regulation of human complement factor h sensitizes non-small cell lung cancer cells to complement attack and reduces in vivo tumor growth
    Ajona, Daniel
    Hsu, Yi-Fan
    Corrales, Leticia
    Montuenga, Luis M.
    Pio, Ruben
    [J]. JOURNAL OF IMMUNOLOGY, 2007, 178 (09) : 5991 - 5998
  • [3] Anti-HSP70 alleviates cell migration and proliferation in colorectal cancer cells (CRC) by targeting CXCR4 (in vitro study)
    Alsaab, Hashem O.
    Almalki, Atiah H.
    [J]. MEDICAL ONCOLOGY, 2023, 40 (09)
  • [4] Breast-cancer stem cells-beyond semantics
    Badve, Sunil
    Nakshatri, Harikrishna
    [J]. LANCET ONCOLOGY, 2012, 13 (01) : E43 - E48
  • [5] Cancer stem cell in breast cancer therapeutic resistance
    Bai, Xupeng
    Ni, Jie
    Beretov, Julia
    Graham, Peter
    Li, Yong
    [J]. CANCER TREATMENT REVIEWS, 2018, 69 : 152 - 163
  • [6] Complement activation, regulation, and molecular basis for complement-related diseases
    Bajic, Goran
    Degn, Soren E.
    Thiel, Steffen
    Andersen, Gregers R.
    [J]. EMBO JOURNAL, 2015, 34 (22) : 2735 - 2757
  • [7] Breast cancer: Biology, biomarkers, and treatments
    Barzaman, Khadijeh
    Karami, Jafar
    Zarei, Zeinab
    Hosseinzadeh, Aysooda
    Kazemi, Mohammad Hossein
    Moradi-Kalbolandi, Shima
    Safari, Elahe
    Farahmand, Leila
    [J]. INTERNATIONAL IMMUNOPHARMACOLOGY, 2020, 84
  • [8] Therapeutic Implications of Cellular Heterogeneity and Plasticity in Breast Cancer
    Brooks, Michael D.
    Burness, Monika L.
    Wicha, Max S.
    [J]. CELL STEM CELL, 2015, 17 (03) : 260 - 271
  • [9] Breast Cancer Stem Cells
    Crabtree, Judy S.
    Miele, Lucio
    [J]. BIOMEDICINES, 2018, 6 (03)
  • [10] Regulation of regulators: Role of the complement factor H-related proteins
    Cserhalmi, Marcell
    Papp, Alexandra
    Brandus, Bianca
    Uzonyi, Barbara
    Jozsi, Mihaly
    [J]. SEMINARS IN IMMUNOLOGY, 2019, 45