Fig. 4

Upstream regulators and downstream biological effects predicted by Ingenuity Pathway Analysis on the proteome level. The “master regulators” of the analyzed dataset were predicted (blue and orange octagons), based on regulated proteins (green and red symbols indicate a fold change > |1.5| and a q-value <0.05) and literature data from the Ingenuity Knowledge Data Base. (a) TGF-β1, SMAD3, and RAC1 were the only upstream regulators predicted to be active, and (b) the estrogen receptor (group) was the only regulator predicted to be inhibited, when the full length syndecan-1 was expressed. (c) Regulated proteins were predicted to lead to a set of downstream biological effects, all pertaining to cell viability. All predicted regulators had a Z-score (activation score) > |1.9|, and a Fisher’s exact p-value < 0.05. Dashed lines are indirect effects, and the shape of the protein indicates the protein class (defined by IPA). Magnitude of regulations: TGF-β1 (Z-score = 2.62, P-value = 1.42e-06), SMAD3 (Z-score = 1.98, P-value = 1.38e-06), RAC1 (Z-score = 1.96, P-value = 2.15e-04), and the estrogen receptor (group) (Z-score = −2.0, P-value = 2.54e-02); proliferation of leukemia cell lines (Z-score = −2.08, P-value = 4.59e-06), proliferation of pancreatic cancer cell lines (Z-score = −1.96, P-value = 3.38e-03), proliferation of smooth muscle cells (Z-score = −1.95, P-value = 5.27e-03); death of epithelial cells (Z-score = 1.99, P-value = 5.96e-04), and apoptosis of connective tissue cells (Z-score = 1.91, P-value = 1.01e-03)