Supplementary Figure 1. A B C MP-MRT-AN KP-MRT-NS KP-MRT-RY KP-MRT-YM

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Supplementary Figure 1. A B C MP-MRT-AN KP-MRT-NS KP-MRT-RY KP-MRT-YM Percentage of CD146+ cells (%) Passage number after cell sorting

Supplementary Figure 2. H&E INI1 ⅰ ii ⅱ ⅲ ⅳ ⅳ ⅴ ⅵ

Supplementary Figure 3. CD146 MP- MRT-AN KP- MRT-RY CD34/CD45/CD31 MRT-YM CD34/CD45/CD31 CD146 First transplantation Second transplantation Third transplantation MP- MRT-AN Supplementary Figure 3. 66.1% 99.0% 99.8% 72.6% 91.7% 97.1% 58.4% 95.0% 99.1%

Supplementary Figure 4. A B C D E CD146 Hoechst33342 Merged kDa 250 - Pre-immune serum Antiserum against CD146 CD146 Hoechst33342 Merged B C kDa 250 - 150 - 100 - 75 - Scramble shRNA CD146 shRNA#2 CD146 β-actin CD146+ cells (KP-MRT-NS) HEK293 CD146− cells (KP-MRT-NS) D E Viable cell (O.D. 450nm) NS Viable cell (O.D. 450nm) NS Hours Hours

Days after cell injection Supplementary Figure 5. A B * Percentage of apoptotic cells (%) Control 10% Rabbit serum Anti-CD146 antiserum * Hours Viable cell (O.D. 450nm) C Days after cell injection D Volume of tumor (mm3) NS * * control 10% Rabbit serum 10% Anti-CD146 antiserum E F * Weight of tumor (mg) PBS Rabbit IgG Anti-CD146 Ab PBS Normal rabbit IgG Anti-CD146　Ab

Supplementary Figure 6. A B p-Akt (Ser473) Akt β-actin 10% Rabbit Scramble shRNA CD146 shRNA#1 CD146 shRNA#2 10% Rabbit serum 10% Anti-CD146 antiserum B p-p38 MAPK (Thr180/Try182) p38　MAPK p-Erk (Thr202/Tyr204) Erk β-actin Scramble shRNA CD146 shRNA#1 CD146 shRNA#2 10% Rabbit serum 10% Anti-CD146 antiserum

Supplementary Figure 7. A B C D * * * * * * * * * * * * * * * * * * * Viable cell (O.D. 450nm) * Viable cell (O.D. 450nm) * * * * * * * * * * * * * * * Hours Hours C D NS * NS * Percentage of apoptotic cells (%) Percentage of Ki-67 positive cells (%) DMSO Rapamycin　 Ku-0063794 DMSO Rapamycin　 Ku-0063794

Supplementary Figure 8. A B * C D * E F * * * Hours YM/pFN28A YM/CD146 HaloTag-CD146 Number of spheres/10000 cells β-actin YM /pFN28A YM /CD146 YM/pFN28A YM/CD146 C D * * * Percentage of apoptotic cells (%) Viable cell (O.D. 450nm) * YM/pFN28A YM/CD146 Hours E F NS p-Akt (Ser473) Akt Percentage of Ki-67 positive cells (%) β-actin YM /pFN28A YM /CD146 YM/pFN28A YM/CD146

Supplementary Figure 9. A B C D * * NS HEK/pFN28A HEK/CD146 HEK/pFN28A Viable cell (O.D. 450nm) Hours * CD146 HaloTag-CD146 β-actin HEK/ pFN28A HEK/ CD146 C D * NS Percentage of Ki-67 positive cells (%) Percentage of apoptotic cells (%) HEK/pFN28A HEK/CD146 HEK/pFN28A HEK/CD146

Supplementary Figure 10. A * * * * * B * * * * * * * Volume of tumor (mm3) * * * * * B Volume of tumor (mm3) * * * * * * *

Supplementary Figure 11. A B C KP-MRT-NS MP-MRT-AN KP-MRT-NS MP-MRT-AN Normal rabbit IgG Anti-CD146 Ab KP-MRT-NS MP-MRT-AN B KP-MRT-NS MP-MRT-AN Normal rabbit IgG Anti-CD146 Ab C Vessel number/mm3 KP-MRT-NS Normal rabbit IgG Anti-CD146 Ab NS MP-MRT-AN NS Vessel number/mm3 Normal rabbit IgG Anti-CD146 Ab

Days after cell injection Supplementary Figure 12. A Days after cell injection Volume of tumor (mm3) * * * B * Weight of tumor (mg) Scramble shRNA CD146 shRNA#1 shRNA#2 C Scramble shRNA CD146 shRNA#1 CD146 shRNA#2

Supplementary Figure 13. ⅰ ⅱ ⅲ ⅳ ⅴ ⅵ H&E INI1 CD146 Patient #11 (relapse)