Supplementary S1 HSC3 HSC3M3 HN5 HN30 H357 UMSCC74A UMSCC74B UMSCC11B

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Supplementary S1 HSC3 HSC3M3 HN5 HN30 H357 UMSCC74A UMSCC74B UMSCC11B Age 63 73 unknown 74 N/A 65 59 Sex M F Origin cervical lymph node/tongue carcinoma metastatic from HSC3 in mice tongue pharynx base of tongue hypopharynx lymph node metastasis/ Tumour differentiation poorly diff. mod. diff. well diff. TNM T2N0M0 T1N0M0 T2N2aM0 T2N1M0 Stage II I V III Prior treatment CT/RT none CT p53 status mutant wild type Ras status HPV status negative

Supplementary S2 SM TRAIL HSC3 0.03 nM - HSC3M3 0.47 nM HN5 0.25 nM 6.7 ng/ml UMSCC74A 2.8 ng/ml UMSCC74B 28.3 ng/ml H357 82.1 ng/ml UMSCC11B 0.77 ng/ml UMSCC22B 110.3 ng/ml

Supplementary S3 SM sensitive TRAIL sensitive HSC3M3 HSC3 HN5 HN30 UMSCC11B UMSCC74A Isotype, TRAIL-R1, TRAIL-R2

Supplemental S4 A B Ctrl scr sh-C8 SM 2h 4h 6h 47 29 59 kDa 42 Casp-10 Casp-10 (cleaved) Actin B Ctrl HSC3 H357 2h 4h 6h TRAIL Casp-10 Casp-10 (cleaved) Actin 59 kDa 47 29 42

SUPPLEMENTAL S5 A C B Ctrl 2h 4h 6h HSC3 H357 SM HSC3 H357 HSC3 H357 89 kDa 34 22 42 19 17 PARP (cleaved) Casp-3 Casp-3 (cleaved) Bid Actin B Cyt c Tubulin scr sh-Bid Ctrl 3h SM 12 kDa 55