Leah B. Zamechek

Figure S10 shows that treatment with the NTN1-neutralizing antibody reduces tumor growth, FAK phosphorylation, and innervation in an mT4 liver metastasis model, improves mouse survival, and decreases tumor burden in a Panc02 liver metastasis model.

Figure S6 shows that Ntn1 knockout decreases innervation, reduces CD11b+ myeloid cells, and increases CD8+ T cells in KPC tumors.

Figure S9 shows that tumoral Neo1 knockout reduces the growth of PDAC liver metastasis in mT4 and Panc02 splenic injection models.

Figure S5 shows that β-adrenergic stimulation increases mT4 PDAC cell growth and migration while upregulating stemness- and EMT-related genes.

Figure S1 shows that Ntn1 and Neo1 are upregulated in mouse pancreatic tumor cells and that high expression of NTN1 and NEO1 is associated with shorter overall survival in patients with PDAC.

Figure S2 shows that KrasG12D mutation and β-adrenergic stimulation upregulate Ntn1 and Neo1 through MAPK pathway-mediated interaction of ELK1 (for Ntn1) or c-JUN (for Neo1) with their promoter regions.

Figure S8 shows that innervation is increased in PDAC liver metastasis and that NTN1 overexpression in Panc02 cells promotes the growth of PDAC liver metastasis in a splenic injection model.

Figure S4 shows that NTN1 enhances PDAC cell migration through NEO1 and upregulates Zeb1 and Sox9 through the NEO1-FAK-AKT axis.

Figure S7 shows that, in an mT4 orthotopic transplantation model, tumoral Ntn1 overexpression increases tumor burden, FAK phosphorylation, and the expression of ZEB1, SOX9, and Ki-67, as well as PGP9.5+ and TH+ nerve density.

Figure S3 shows that tumoral NTN1 overexpression promotes neurite outgrowth of celiac ganglia in a co-culture model, while Ntn1 knockout inhibits adrenergic innervation in KC mice.