|Table of Contents|

C1ql4 regulates the characteristics of breast cancer stem cells and epithelial-mesenchymal transition through PI3K/Akt signaling pathway

Journal Of Modern Oncology[ISSN:1672-4992/CN:61-1415/R]

Issue:
2023 16
Page:
2977-2982
Research Field:
Publishing date:

Info

Title:
C1ql4 regulates the characteristics of breast cancer stem cells and epithelial-mesenchymal transition through PI3K/Akt signaling pathway
Author(s):
XU FanZHANG QingLI Xiao
Department of Oncology,Affiliated Hospital of Chengde Medical University,Hebei Chengde 067000,China.
Keywords:
breast cancerC1ql4migrationepithelial-mesenchymal transitionapoptosisPI3K/Akt
PACS:
R737.9
DOI:
10.3969/j.issn.1672-4992.2023.16.006
Abstract:
Objective:To explore the effects of C1ql4 on the characteristics of breast cancer stem cells and the epithelial mesenchymal transition.Methods:siRNA interference technique was used to down-regulate the expression of C1ql4 in BT549 cell line.RT-qPCR and Western blot methods were used to verify the silence of C1ql4.The subsequent experiments were divided into control group,empty vector group(si-NC group) and C1ql4 silence group(si-C1ql4 group).The mRNA and protein expression of stem cell characteristic-related protein(CD44,Nanog,OCT4) and EMT-related proteins(E-cadherin,Vimentin,N-cadherin) in each group were detected,respectively.The apoptosis,CD44+CD24-/low cell content of cells in each group were detected by flow cytometry,and the spheroidizing ability of cells in each group was compared by spheroidizing test,and the migration ability of cells in each group was compared by Transwell chamber test.Western blot was used to detect the expression level of signal pathway proteins,and explore the possible mechanism of C1ql4 affecting the characteristics of breast cancer stem cells and epithelial mesenchymal transformation.Results:After down-regulation of C1ql4 expression,the mRNA and protein expression of CD44,Nanog,OCT4,Vimentin and N-cadherin,breast cancer stem cell ratio,balling and migration ability of si-C1ql4 group were lower than those of control group and si-NC group,while the expression of E-cadherin mRNA and protein,apoptosis rate were significantly higher than those of the other two groups.The protein expression level and phosphorylation level of PI3K and Akt were also significantly lower than those of control group and si-NC group(P<0.05),but there was no significant difference between control group and si-NC group.Conclusion:The expression of C1ql4 can promote the expression of breast cancer stem cells and the epithelial mesenchymal transformation,enhance the biological behavior of breast cancer cells such as spheroidization and migration,inhibit cell apoptosis.The mechanism of action may be related to PI3K/Akt signaling pathway.

References:

[1]SUNG H,FERLAY J,SIEGEL RL,et al.Global cancer statistics 2020:GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J].A Cancer Journal for Clinicians,2021,71(3):209-249.
[2]ALLEMANI C,MATSYDA T,DI CARLOV,et al.Global surveillance of trends in cancer survival 2000-14(CONCORD-3):analysis of individual records for 37 513 025 patients diagnosed with one of 18 cancers from 322 population-based registries in 71 countries[J].Lancet,2018,391(10125):1023-1075.
[3]AL-HAJJ M,WICHA MS,CLARK MF,et al.Prospective identification of tumorigenic breast cancer cells[J].Proceedings of the National Academy of Sciences of the United States of America,2003,100(7):3983-3988.
[4]SCHEEL C,WEINBERG RA.Cancer stem cells and epithelial-mesenchymal transition:concepts and molecular links[J].Seminars in Cancer Biology,2012,22(6):396-403.
[5]ANSIEAU S.EMT in breast cancer stem cell generation[J].Cancer Letters,2013,338(1):63-68.
[6]THIELENS NM,TEDESCO F,BOHLSON SS,et al.C1q:A fresh look upon an old molecule[J].Molecular Immunology,2017,89:73-83.
[7]FAN MY,XIONG XF,HAN L,et al.SERPINA5 promotes tumour cell proliferation by modulating the PI3K/AKT/mTOR signalling pathway in gastric cancer[J].Journal of Cellular and Molecular Medicine,2022,26(18):4837-4846.
[8]REYA T,MORRISON SJ,CLARKE MF,et al.Stem cells,cancer,and cancer stem cells[J].Nature,2001,414(6859):105-111.
[9]LIJIMA T,MIURA E,WATANABE M,et al.Distinct expression of C1q-like family mRNAs in mouse brain and biochemical characterization of their encoded proteins[J].European Journal of Neuroscience,2010,31(9):1606-1615.
[10]WANG X,ZHOU R,XIONG Y,et al.Sequential fate-switches in stem-like cells drive the tumorigenic trajectory from human neural stem cells to malignant glioma[J].Cell Research,2021,31(6):684-702.
[11]刘芳.C1ql1和C1ql4促进新生血管形成的机制研究[D].广州:暨南大学,2016. LIU F.The mechanisms of C1ql1 and C1ql4 on proangiogenesis [D].Guangzhou:Jinan University,2016.
[12]TAN A,KE S,YU Y,et al.Expression patterns of C1ql4 and its cell-adhesion GPCR Bai3 in the murine testis and functional roles in steroidogenesis[J].FASEB Journal,2019,33(4):4893-4906.
[13]WEI Z,SELDIN MM,WONG JM,et al.C1q/tumor necrosis factor-related protein 11(C1QL4),a novel adipose stroma-derived regulator of adipogenesis[J].The Journal of Biological Chemistry,2013,288(15):10214-10229.
[14]WANG X,CHEN S,SHEN T,et al.Trichostat in a reverses epithelial-mesenchymal transition and attenuates invasion and migration in MCF-7 breast cancer cells[J].Experimental and Therapeutic Medicine,2020,19(3):1687-1694.
[15]李洋,邢瑶,韩馥伊,等.PAK5通过上皮-间质转化促进人乳腺癌细胞侵袭[J].现代肿瘤医学,2018,26(23):3705-3708. LI Y,XING Y,HAN FY,et al.PAK5 promotes invasion of human breast cancer cells through epithelial-mesenchymal transition[J].Modern Oncology,2018,26(23):3705-3708.
[16]DAVID SARRIO,SOCORRO MARIA RODRIGUEZ-PINILLA,DAVID HARDISSON,et al.Epithelial-mesenchymal transition in breast cancer relates to the basal-like phenotype[J].Cancer Research,2008,68(4):989-997.
[17]PARK SY,LEE HE,LI H,et al.Heterogeneity for stem cell-related markers according to tumor subtype and histologic stage in breast cancer[J].Clinical Cancer Research,2010,16(3):876-887.
[18]ZOU W,YANG Y,ZHENG R,et al.Association of CD44 and CD24 phenotype with lymph node metastasis and survival in triple-negative breast cancer[J].International Journal of Clinical and Experimental Pathology,2020,13(5):1008-1016.
[19]NEWIE I,SOKILDE R,PERSSON H,et al.The HER2-encoded miR-4728-3p regulates ESR1 through a non-canonical internal seed interaction[J].PLoS One,2014,9(5):e97200.

Memo

Memo:
河北省自然科学基金项目(编号:H2021406036);河北省承德市应用技术研究与开发暨可持续发展议程创新示范区专项科技计划项目(编号:202205B073)
Last Update: 1900-01-01