Supplementary Figure S1: FRS2 Copy Number and Gene Expression Analysis in NRH-LS1, LPS510 and LPS853 Cells, and Ls70x Xenograft

A B

LS70x LS70x

C FRS2/Tubulin NRH-LS1 LPS510 LPS853 LS70x 4,000 3,433 o n Ɵ a

c 3,000 Į

FRS2 Ɵ n a

u 2,000 Q

1,132 1,191 e v

Ɵ 1,000 0,467 a Tubulin l e R 0,000 NRH-LS1 LPS510 LPS853 LS70x

Supplementary Figure S1: FRS2 Copy Number and Gene Expression Analysis in NRH-LS1, LPS510 and LPS853 cells, and LS70x xenograft. A, The number of FRS2 gene copies relative to LSAMP; one representative experiment is shown (n=3), error bars represent standard deviation (SD) of technical replicates. B, Relative gene expression of FRS2 compared to B2M relative to human adipose tissue; error bars represent standard deviation (SD) of experiments (n=2, iMSC#3 n=1). C, Western blot with quanti cation showing the total FRS2 levels in the three cell lines and the LS70x xenograft. A B

6,9315 46,473

C D

21,2452 5,4707

Supplementary Figure S2: LY2874455 has better e cacy than NVP-BGJ398. A, The IC50 was estimated for NRH-LS1 treated with NVP-BGJ398 at 46 nM. B, The IC50 was estimated for NRH-LS1 treated with LY2874455 at 7 nM. C, The IC50 was estimated for LPS510 treated with NVP-BGJ398 at 21 nM. D, The IC50 was estimated for LPS510 treated with LY2874455 at 5 nM. A-D, Cell viability measured by relative ATP levels to untreated after 120h of treatment. NRHLS1 LPS510 LPS853

FRS2 FGFR F FGFR1 FGFRL1

FGFR4 amily FGFR3 FGFR2 FGF2 FGF11 FGF7 FGF5 FGF1 FGF13 FGF18 FGF16 FGFR Ligands FGF17 FGF9 FGF12 FGF19 FGF22 FGF21 FGF10 FGF14 FGF8 FGF20 FGF6 FGF4 FGF3 FGF23 NGFRAP1

MAP2K2 Adapter Proteins MAP2K1 AKT1 GRB2 FPKM MAPK3 200 MAPK1 NRAS 150 PLCG1 PIK3CA 100 AXL MUSK 50 PDGFRA RORA 0 RYK EPHA2 DDR2 ERBB2 EGFR IGF1R DDR1 PDGFRB KIT T

ROR1 yrosine Kinase Receptors EPHA4 INSR NGFR LTK FLT4 EPHA7 TEK EPHA3 ALK ERBB3 FLT1 RET EPHA6 EPHA10 ROS1 ROR2 EPHA5 CSF1R KDR EPHA1 FLT3 ERBB4 EPHA8 Supplementary Figure S3: Heatmap of expression of FGFR pathway genes and other tyrosine kinases between NRH-LS1, LSP510 and LPS853 cell lines. Relative expression levels (FKPMs) for each gene is presented in separate panels showing FGFRs and FRS2 (top panel), FGF ligands, adapter proteins downstream in the FGF pathway (except for NGFRAP1), and other tyrosine kinase receptors. Genes are sorted by FPKM values in each panel. A

pFRS2/FRS2 pAKT/AKT pERK/ERK pPLCȖ/PLCȖ 1,20 4,50 4,16 0,60 0,55 0,12 1,06 1,06 0,12 4,00 1,00 0,50 o n o n o n 0,89 3,50 Ɵ Ɵ o n Ɵ a a a 0,10 Ɵ c c c

a 3,00 0,40 Į Į Į c 0,80 0,70 Ɵ Ɵ Į Ɵ n n n 0,08 Ɵ 0,64 2,50 a a a n u u u a 0,30 u Q Q Q 0,60

0,06 2,00 1,65 Q e e e

v v v e Ɵ Ɵ v Ɵ 1,50 1,15 0,20 a a a Ɵ l l l 0,04 0,40 a e e e l R R R 1,00 e 0,62 0,02 R 0,10 0,50 0,26 0,19 0,02 0,03 0,03 0,00 0,20 0,02 0,02 0,00 0,00 0,00 NRH-LS1 NRH-LS1 + NRH-LS1 + NRH-LS1 + NRH-LS1 + NRH-LS1 + 0,00 NRH-LS1 NRH-LS1 + NRH-LS1 + NRH-LS1 + NRH-LS1 + NRH-LS1 + NRH-LS1 NRH-LS1 + NRH-LS1 + NRH-LS1 + NRH-LS1 + NRH-LS1 + FGF NVP- LY2874455 NVP- LY2874455 NRH-LS1 NRH-LS1 + NRH-LS1 + NRH-LS1 + NRH-LS1 + FGF NVP- LY2874455 NVP- LY2874455 FGF NVP- LY2874455 NVP- LY2874455 BGJ398 BGJ398 + + FGF FGF NVP-BGJ398 LY2874455 NVP-BGJ398 + BGJ398 BGJ398 + + FGF BGJ398 BGJ398 + + FGF FGF FGF FGF FGF

B pFRS2/FRS2 pAKT/AKT 0,7 5,00 4,38 0,60 4,50 0,6 4,08 4,00 o n o n 3,47 Ɵ 0,5 Ɵ 3,28 a a 3,50 3,14 c c 3,08 Į 0,41 Į Ɵ Ɵ 3,00 n 0,4 n 2,52 a a 2,26 u u 2,50 Q Q

0,3 e e 2,00 v v Ɵ Ɵ a a l 0,2 l 1,50 e e 0,96 R R 1,00 0,83 0,70 0,1 0,06 0,37 0,50 0,00 0,00 0 0,00 NRH-LS1 NRH-LS1 + NRH-LS1 + NRH-LS1 + LPS510 LPS510 + LPS510 + LPS510 + LPS853 LPS853 + LPS853 + LPS853 + NRH-LS1 NRH-LS1 + NRH-LS1 + NRH-LS1 + LPS510 LPS510 + LPS510 + LPS510 + LPS853 LPS853 + LPS853 + LPS853 + FGF LY2874455 FGF + FGF LY2874455 FGF + FGF LY2874455 FGF + FGF LY2874455 FGF + FGF LY2874455 FGF + FGF LY2874455 FGF + LY2874455 LY2874455 LY2874455 LY2874455 LY2874455 LY2874455

pERK/ERK pPLCȖ/PLCȖ 2,50 0,80 2,18 0,71 0,70 2,00 1,83 o n o n 0,60 0,54 Ɵ Ɵ a a c c 0,48 Į Į 0,50 Ɵ 1,50 Ɵ n n a a u u 0,40 Q 0,98 Q

e 1,00 e v v 0,30 Ɵ 0,69 0,65 Ɵ a a l l e e 0,20 R 0,50 R 0,11 0,18 0,10 0,10 0,04 0,04 0,04 0,08 0,05 0,09 0,03 0,02 0,03 0,02 0,01 0,01 0,01 0,00 0,00 NRH-LS1 NRH-LS1 + NRH-LS1 + NRH-LS1 + LPS510 LPS510 + LPS510 + LPS510 + LPS853 LPS853 + LPS853 + LPS853 + NRH-LS1 NRH-LS1 + NRH-LS1 + NRH-LS1 + LPS510 LPS510 + LPS510 + LPS510 + LPS853 LPS853 + LPS853 + LPS853 + FGF LY2874455 FGF + FGF LY2874455 FGF + FGF LY2874455 FGF + FGF LY2874455 FGF + FGF LY2874455 FGF + FGF LY2874455 FGF + LY2874455 LY2874455 LY2874455 LY2874455 LY2874455 LY2874455

C LS70x

FRS2/Tubulin pERK/Tubulin pERK/ERK 0,284 3,000 0,035 0,032 0,031 0,300 0,267 0,275 2,540 o n o n 2,500 0,030 o n 0,250 0,234 Ɵ Ɵ Ɵ a a a c c 0,025 0,022 c 0,194 Į Į 2,000 Į 0,200 Ɵ Ɵ 1,663 0,019 Ɵ n n 0,020 n a a 1,306 1,358 0,016 a 0,130 0,136 u u 1,500 1,164 1,137 u 0,150

1,102 Q Q 0,012 0,012 Q 0,015 0,994 e e 0,009 e

v 0,077 v 1,000 0,689 0,008 v 0,100 0,075

Ɵ 0,010 Ɵ Ɵ

0,488 a a a

l 0,043 l 0,005 l e e 0,500 0,005 e 0,050 R R R 0,000 0,000 0,000

Supplementary Figure S4: Quanti cations of western blots from Figure 4A (A), Figure 4B (B), and Figure 5B (C).