Fig 2: Bidirectional PSAP-TGFβ1 Paracrine Signaling Sustains SCs–GC Crosstalk. A Schematic of paracrine communication between SCs and GC Cells. B The secretion of PSAP by GC cells increased after co-culture with SCs. C TGFβ1 expression was increased in SCs co-cultured with GC cells and treated with rPSAP. D TGFβ1 secretion was increased in SCs co-cultured with GC cells and treated with rPSAP. E–F The secretion and expression of PSAP in GC cells treated with rTGFβ1 were increased. G-H The TGFβ1 inhibitor (Asiaticoside) can inhibit the effect of rTGFβ1 on the secretion and expression of PSAP

Fig 3: Therapeutic Targeting of PSAP/TGFβ1 Suppresses PNI In Vivo. A Inhibition of PSAP/TGFβ1 reduces PNI Incidence DRG-PNI model in vitro. B Schematic of a Sciatic Nerve Invasion Murine Model. C-D Tumor formation and H&E and IHC detection in the sciatic nerve model. E–F Functional and physiological assessments post intervention (Sciatic Nerve Score, Body Weight). G GMulticolor IF was used to verify the spatial distribution of PSAP, TGFβ1 and SCs(S100β) in PNI-positive tumor tissues

Fig 4: TGFβ1 Engages the TGFβ1/Smad4/Sortilin Axis to Amplify PSAP Secretion and PNI. A Schematic representation of TGFβ1 secreted by SCs acting on GC cells. B In vitro PNI assays showed that downregulation of SCs-derived TGF-β1 diminished GC cell PNI. C-E Asiaticoside can inhibit the effects of rTGFβ1 on the proliferation, invasion and PSAP secretion of GC cells. F Schematic representation of PSAP secretion. G TGFβ1/Smad4 signaling activation induces increased PSAP secretion through the suppression of Sortilin expression. H Dual-luciferase and ChIP-qPCR analyses showed that Smad4 binds the Sortilin promoter and represses its transcription, linking TGF-β1/Smad4 activation to Sortilin downregulation. I Sortilin overexpression suppresses PSAP secretion

Fig 5: SCs-Induced PSAP Overexpression Potentiates GC Malignancy. A Venn analysis of differentially expressed proteins (DEPs) in the co-culture system. B IHC validation of PSAP upregulation in PNI-positive GC tissues. C Western Blot (WB) confirm PSAP Induction in co-cultured GC cells. D PSAP augments migration, invasion, and clonogenic capacity of GC cells. E–F The possible interacting proteins of PSAP were analyzed by co-immunoprecipitation and mass spectrometry. G Pull-down assay was used to verify the interaction of PSAP-CTSD-GALC. H Scanning electron microscopy was used to detect autophagosomes. I Inhibition of Autophagy Mediated by the PSAP–CTSD–GALC Complex. J mRFP-GFP-LC3B adenovirus reporter was used to detect autophagic flux. K Autophagic flux inhibition attenuates tumor-promoting effects of PSAP overexpression