Supplementary Figure S1 (Mishra et al )

1. Time (min) 0 5 10 15 30 45 a c 1 2 3 4 5 6 1 2 3 4 5 6 1 2 3 4 5 6 1 2 3 4 5 6 Mw (kDa) Foxo 3a 64 50 Foxo 3a pAkt Foxo 3a Probe-1 Cold Probe-1 (25X) Probe-2 Akt Wt Mut FP FP 64 50 Foxo 3a MDA-MB-231 Free probe Sema 3A - + + + + + (100 ng/ml) e Free probe b Time (min) 0 30 45 90 180 240 Sema 3A - + + + + + (100 ng/ml) Sema 3A (100 ng/ml) Coni NRP1i NRP1 neu Ab (5µg/ml) NRP1 block pep (20 µg/ml) - - + + + + - + - - - - - - - + - - - - - - + - - - - - - + Sema 3A (100 ng/ml) Coni PTENi dnPTEN wt PTEN - - + + + + - + - - - - - - - - + - - - - - - + - - - + - - Free probe d MDA-MB-231 MDA-MB-231 MDA-MB-231 1 2 3 4 5 Free probe MDA-MB-231 Supplementary Figure S1 (Mishra et al)

2. a MDA-MB-231 b Sema 3A + dn PTEN f 0 h Sema 3A + wt PTEN Sema 3A + PTENi d Coni Sema 3A e a b c Control 16 h Control Sema 3A + dn PTEN Coni Sema A + PTENi Sema 3A + wt PTEN Sema 3A MDA-MB-231 Supplementary Figure S2 (Mishra et al)

3. a c e a b d f Control Coni Sema 3A Sema 3A + Foxo 3a TM Sema 3A + wt Foxo 3a Sema 3A + Foxo 3ai MDA-MB-231 b 0 h 16 h Control Sema 3A Coni Sema 3A+ wt Foxo 3a Sema 3A + Foxo 3ai Sema 3A + Foxo 3a TM MDA-MB-231 Supplementary Figure S3 (Mishra et al)

4. a 0 h e Sema 3A + NRP1 block pep MDA-MB-231 b c f b d 16 h Sema 3A + NRP1i Control Coni Sema 3A Sema 3A+ NRP1 neu Ab Sema 3A + NRP1 block pep MDA-MB-231 a Coni Control Sema 3A Sema 3A + NRP1i Sema 3A + NRP1 neu Ab Supplementary Figure S4 (Mishra et al)

5. b HUVEC (Upper chamber) a NRP1i NRP1 neu Ab NRP1 block pep I I Co-invasion Co-migration Co-migration d b HUVEC (Upper chamber) II Medium rhSema 3A + NRP-1 neu Ab f a e Coni rhSema 3A rhSema 3A + NRP-1i c e a d c b II CM MDA-MB-231 cells (Lower chamber) e c b d f a Medium Coni rhSema 3A rhSema 3A rhSema 3A rhSema 3A Co-invasion b a c d HUVEC e c * ## ** ** migration/invasion (% Control) # * CM MDA-MB-231 cells (Lower chamber) CM MDA-MB-231 + rh Sema 3A NRP-1 neu Ab Coni NRP-1i Medium Supplementary Figure S5 (Mishra et al) CM MDA-MB-231 + rh Sema 3A (Lower chamber)

6. c 0 h 24 h Control Sema 3A block pep (20μg/ml) MCF-7 a b 0 h MDA-MB-231 MDA-MB-231- Sema 3A a b 16 h MDA-MB-231 MDA-MB-231- Sema 3A Supplementary Figure S6 (Mishra et al)

7. d a Medium 0 h 48 h g f a b c e d rhVEGF + rhSema 3A + NRP1 neu Ab Medium rhVEGF rhVEGF * b ** ** a ** b ** rhSema 3A * ** Tube length (% Control) Change in length and size c rhVEGF + rhSema 3A d c rhVEGF + NRP1 neu Ab rhVEGF + rhSema 3A rhSema 3A • - + - + + + + • + - - - - - - • - - - + + - • - + + - + - • - - - - - - + VEGF (50 ng/ml) Medium NRP1 neu Ab (5 µg/ml) Sema 3A (100 ng/ml) CM MDA-MB-231-Sema 3A rhVEGF Medium rhVEGF + rhSema 3A rhSema 3A e f g h rhVEGF + CM MDA-MB-231 -Sema 3A Supplementary Figure S7 (Mishra et al)

8. a c d MCF-7-Sema 3A shRNA FOXO3A Sema 3A Ki67 MCF-7-mock vector i i ii ii b CD31/DAPI pPTEN Probability n=2878 iii iv iii iv VEGF Relapse free survival (years) pFoxo 3a vi v MCF-7- Sema 3A block pep MCF-7 vi v Foxo 3a vii viii e MelCAM ix x MCF-7- Sema 3A block pep MCF-7 MCF-7 MCF-7-Sema 3A block pep (1 mg/Kg body weight) Supplementary Figure S8 (Mishra et al)

9. Correlation between Sema 3A & pPTEN with breast cancer progression Supplementary Table S1 (Mishra et al )