The m6A modification mechanism of BAK1 and its role in anoikis of breast cancer cells

ZHANG Yunjiao; ZHANG Bo; WANG Jiajia; ZHANG Xue; CHEN Xi; LING Rui; ZHANG Jian

doi:10.13276/j.issn.2097-1656.2025.07.009

Abstract：Objective To investigate the m6A modification mechanism of BAK1 and its role in anoikis of breast cancer cells,in order to elucidate the molecular mechanisms of anoikis resistance and provide new therapeutic targets for breast cancer.Methods An anoikis model was established using low-adhesion culture methods.Cell samples were collected for subsequent experiments after 0,24,48,and 72 h of low-adhesion treatment.Triple-negative breast cancer cells(MDA-MB-231)and non-triple-negative breast cancer cells(T47D)were used as research subjects.Apoptosis rates were detected by Annexin V-FITC/PI double staining,changes in m6A levels were measured by Dot blot assays,and the expression levels of related proteins and genes were analyzed by Western blotting and qRT-PCR.Results T47D had significantly increased apoptosis rates after low-adhesion treatment(P＜0.01),while MDA-MB-231 exhibited strong anoikis resistance.Anoikis induced an increase in m6A levels in non-triple-negative breast cancer cells(P＜0.01),mainly mediated by changes in the expression of the demethylase FTO.Inhibition of m6A modification significantly enhanced the anoikis resistance of breast cancer cells(P＜0.05),and m6A modification affected apoptosis sensitivity by regulating the expression of BAK1.Conclusion This study reveals the important role of m6A modification in anoikis of breast cancer cells and its mechanism through regulating BAK1 expression,providing a new perspective for understanding the invasion and metastasis mechanisms of breast cancer cells and potentially offering a theoretical basis for developing new therapeutic strategies and prognostic biomarkers.