Tigilanol Tiglate-Induced Changes in Secretome Profiles Alter C-Met Phosphorylation and Cell Surface Protein Expression in H357 Head and Neck Cancer Cells.

ABSTRACT: Tigilanol tiglate (TT, also known as EBC-46) is a novel, plant-derived diterpene ester possessing anticancer and wound-healing properties. Here, we show that TT-evoked PKC-dependent S⁹⁸⁵ phosphorylation of the tyrosine kinase MET leads to subsequent degradation of tyrosine phosphorylated p-Y¹⁰⁰³ and p-Y^1234/5 MET species. PKC inhibition with BIM-1 blocked S⁹⁸⁵ phosphorylation of MET and led to MET cell surface accumulation. Treatment with metalloproteinase inhibitors prevented MET-ECD release into cell culture media, which was also blocked by PKC inhibitors. Furthermore, unbiased secretome analysis, performed using TMT-technology, identified additional targets of TT-dependent release of cell surface proteins from H357 head and neck cancer cells.

SUBMITTER: Antwi FD 

PROVIDER: S-EPMC11171882 | biostudies-literature | 2024 Jun

REPOSITORIES: biostudies-literature