Isotoosendanin exerts inhibition on triple-negative breast cancer through abrogating TGF-β-induced epithelial–mesenchymal transition via directly targeting TGFβR1

• DOI: 10.1016/j.apsb.2023.05.006
• Publication Date: 2023-05-12T01:53:41Z
• Authors: Jingnan Zhang; Ze Zhang; Zhenlin Huang; Manlin Li; Fan Yang; Zeqi Wu; Qian Guo; Xiyu Mei; Bin Lu; Changhong Wang; Zhengtao Wang; Lili Ji
• Keywords: Triple-negative breast cancer; Invadopodia

As the most aggressive breast cancer, triple-negative cancer (TNBC) is still incurable and very prone to metastasis. The transform growth factor β (TGF-β)-induced epithelial–mesenchymal transition (EMT) crucially involved in metastasis of TNBC. This study reported that a natural compound isotoosendanin (ITSN) reduced TNBC by inhibiting TGF-β-induced EMT formation invadopodia. ITSN can directly interact with TGF-β receptor type-1 (TGFβR1) abrogated kinase activity TGFβR1, thereby blocking TGF-β-initiated downstream signaling pathway. Moreover, ITSN-provided inhibition on obviously disappeared TGFβR1-overexpressed cells vitro as well mice bearing overexpressed TGFβR1. Furthermore, Lys232 Asp351 residues domain TGFβR1 were found be crucial for interaction Additionally, also improved inhibitory efficacy programmed cell death 1 ligand (PD-L1) antibody vivo via TGF-β-mediated tumor microenvironment. Our findings not only highlight key role metastasis, but provide leading targeting treatment this points out potential strategy using combined application anti-PD-L1 inhibitor.