BAG3
protein is an apoptosis inhibitor and is highly expressed in
Anaplastic Thyroid Cancer. We investigated the entire set of
proteins modulated by BAG3 silencing in the human anaplastic thyroid 8505C
cancer cells by using the Stable-
Isotope Labeling by
Amino acids in Cell culture strategy combined with mass spectrometry analysis. By this approach we identified 37 up-regulated and 54 down-regulated
proteins in BAG3-silenced cells. Many of these
proteins are reportedly involved in
tumor progression, invasiveness and resistance to
therapies. We focused our attention on an oncogenic
protein, CAV1, and a
tumor suppressor protein, SERPINB2, that had not previously been reported to be modulated by BAG3. Their expression levels in BAG3-silenced cells were confirmed by qRT-PCR and western blot analyses, disclosing two novel targets of BAG3 pro-
tumor activity. We also examined the dataset of
proteins obtained by the quantitative proteomics analysis using two tools, Downstream Effect Analysis and Upstream Regulator Analysis of the Ingenuity Pathways Analysis software. Our analyses confirm the association of the
proteome profile observed in BAG3-silenced cells with an increase in cell survival and a decrease in cell proliferation and invasion, and highlight the possible involvement of four
tumor suppressor
miRNAs and TP53/63
proteins in BAG3 activity.