Alterations in S6K1 isoform expression in MCF-7 cells that induce EMT, affect Akt1–, AMPK–, PKC–, and PKA-related cell signaling

Martsynyuk, M. Ye.; Gotsulyak, N. Ya.; Filonenko, V. V.

doi:10.7124/bc.000B26

Biopolym. Cell. 2025; 41(4):251.

http://dx.doi.org/10.7124/bc.000B26

Structure and Function of Biopolymers

Alterations in S6K1 isoform expression in MCF-7 cells that induce EMT, affect Akt1–, AMPK–, PKC–, and PKA-related cell signaling

1Martsynyuk M. Ye., 1Gotsulyak N. Ya., 1Filonenko V. V.

Institute of Molecular Biology and Genetics, NAS of Ukraine
150, Akademika Zabolotnoho Str., Kyiv, Ukraine, 03143

Abstract

Aim. This study aimed to evaluate how S6K1 isoform expression affects the activities of Akt1, AMPK, PKC, and PKA, as well as their related kinase signaling pathways. Methods. MCF-7 cells and a subline with disrupted p70 and p85 S6K1 isoform expression (MCF7/p60+/p70–/p85–) were cultured under different growth conditions. Western blot analysis was performed on cell lysates using antibodies specific to phosphorylated substrates of Akt1, AMPK, PKC, PKA, and GSK-3β/pSer9. Results. The phosphorylation pattern of kinase substrates showed that changes in S6K1 isoform expression influenced either the activity of Akt1, AMPK, PKC, PKA, or their substrate specificity. Unexpectedly, in the MCF-7 subline exhibiting EMT features, GSK-3β kinase – an Akt1 substrate and EMT inhibitor – was not downregulated by phosphorylation of Ser9. Conclusions. S6K1, a ribosomal protein kinase involved in EMT regulation, can modulate the activity of Akt1, AMPK, PKC, PKA, and GSK-3β, as well as their substrate specificity; therefore, all these kinases may be involved in EMT regulation. GSK-3β could also have a bifunctional role in EMT progression initiated by changes in S6K1 isoform expression that modulate its activity.

Keywords: EMT, MCF7 cell line, S6K1, Akt1, AMPK, PKC, PKA, GSK-3β

Full text: (PDF, in English)

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