SYK-dependent regulation of the AKT1/E-cadherin axis modulates invasion and migration in the Luminal A breast cancer

Background The SYK-AKT1/E-cadherin regulatory axis exhibits subtype-restricted functional pleiotropy in breast cancer pathogenesis. However, its opposing oncogenic versus tumor-suppressive roles across molecular subtypes reflect a functional dichotomy whose molecular determinants remain incompletely defined. This study elucidates the subtype-specific mechanisms by which this axis modulates breast cancer cell invasion and migration. Methods Pan-cancer SYK expression analysis across 33 TCGA tumor types was integrated with gene set enrichment analysis (GSEA). SYK was depleted by siRNA or overexpressed via pEX-3-SYK transfection in Luminal A (MCF-7) and Basal-like (MDA-MB-231) cell lines. Immunoblotting quantified SYK, PI3K/AKT effectors (p-AKT1 ^Ser473 , p-mTOR), and EMT markers (E-cadherin, N-cadherin). Apoptosis and cell cycle distribution were assessed by flow cytometry; Transwell assays measured invasive capacity. Results SYK/AKT1 co-overexpression is an independent prognostic biomarker predicting poor overall survival in Luminal A breast cancer. Mechanistically, SYK upregulation correlated inversely with AKT1, p-AKT1 ^Ser473 , and E-cadherin protein abundance in Luminal A models, concomitant with attenuated PI3K/AKT activation, migration, and invasion. Conversely, SYK overexpression enhanced motility in Basal-like models, revealing context-dependent functional antagonism. Conclusions Collectively, these data establish the SYK-AKT1 axis as a subtype-selective regulator of EMT in Luminal A breast cancer, rationalizing combinatorial pharmacologic inhibition of SYK and PI3K/AKT.