S6K1调控的蛋白表达图谱及其对乳腺癌细胞恶性表型的影响

doi:10.3969/j.issn.1004-616x.2024.03.003

Abstract

Abstract: OBJECTIVE：To investigate the expression and regulation of the ribosomal protein S6 kinase β-1(S6K1) on the malignant phenotype of breast cancer cells. METHODS：Amplification and expression of S6K1 in breast cancer tissues were analyzed by cBioPortal and GEPIA databases，and their relationships with clinical characteristics of the breast cancers were also analyzed. Small interfering RNA was employed to knock down S6K1 in the breast cancer MCF7 cells in vitro to investigate its impact on protein expression profile using mass spectrometry，stemness of breast cancer cells using the sphere formation assay，and migration ability using the migration assay. RESULTS：S6K1 gene exhibited frequent amplification in breast cancer tissues，with a higher amplification rate in invasive compared with non-invasive breast cancers (P<0.05)，and with significant relationship to poor prognosis of patients (P<0.01). In addition，the expression was higher in breast cancer tissues compared with adjacent tissues (P<0.01)，while the expression levels did not differ significantly among different stages of breast cancer (P>0.05). Mass spectrometry revealed 251 upregulated and 224 downregulated proteins following the S6K1 knockdown in the MCF7 cells. GO pathway enrichment analysis indicated that S6K1 regulated the expression of multiple proteins involved in biological processes such as cytoplasmic translation，protein stabilization，stem cell population maintenance，and cell migration. Additional assays demonstrated that S6K1 knockdown significantly inhibited the stemness phenotype and migration ability of breast cancer cells (P<0.05). CONCLUSION：S6K1 regulated the expression of proteins involved in multiple biological processes in breast cancer cells in vivo，and the knockdown of S6K1 significantly inhibited the stemness and migration ability of breast cancer cells in vitro，indicating a crucial regulatory role for S6K1 and highlighting its potential as a novel therapeutic target for breast cancer therapy.

Key words: S6K1, breast cancer, stemness of cells, migration, proteomics

CLC Number:

R737.9

SHU Xingmei, SHI Xiaoqian, LIU Yan, LI Dan. Expression of ribosomal protein S6K1 and its regulation on malignant phenotypes in breast cancer cells[J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2024, 36(3): 179-186,223.

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Expression of ribosomal protein S6K1 and its regulation on malignant phenotypes in breast cancer cells

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