Fig. 10.

Schematic model for the role of PDPN in EMT-related gene expression in TE11A cells. a In TE11A cells, at least three signaling pathways (signaling module 1–3) are involved in the induction of EMT gene expression. The binding of PDPN to CLEC-2 activates signaling module 1 and results in the release of TGF-β from platelets (event 0), which in turn activates signaling module 2. Platelets also activate other signaling pathways (signaling module 3). The activation of signaling module 2 plus module 1 and/or 3 synergistically induces the expression of Vimentin and N-cadherin proteins. b Potential signaling pathways activated by TGF-β. TGF-β activates only signaling module 2, resulting only in the mRNA expression of Vimentin and N-cadherin. c The impact of PDPN knockout on EMT gene expression at resting state and after treatment with TGF-β or platelets. A decrease in the PDPN levels causes spontaneous N-cadherin protein expression, decrease in claudin-1 expression, and prepares the cell to transition into a mesenchymal state (“Ready-to-EMT”) fully in clone 2 cells, but incompletely in clone 4 cells. Half-deficient PDPN clone 2 cells can still interact with platelets and further undergo EMT, however, completely PDPN deficient clone 4 cells cannot (see “Discussion” for more details)