1. Ratio Frequency 0246810 0 20 30 40 50 60 Supplemental Figure S1 : A representative histogram showing the distribution of the incorporation ratios in proteins from the muscle tissue surrounding the xenograft tumor at day 30.

2. Log2(Ratio/Ratio ) Frequency -4-2024 0 100 200 300 400 500 Label Free Log2(Intensity/Intensity ) Frequency -4-2-2 024 0 100 200 300 400 500 Metabolic Labelling Supplemental Figure S2 : Histogram presenting the comparison between Metabolic Labeling and Label Free. Heavy and light tumors were mixed and analyzed by two different LC-MS/MS runs. For metabolic labeling quantification, ratio of proteins between both replicates was estimated using the ratio of ratios calculated by MaxQuant. For label-free quantification, ratio of protein intensities (sum of peptides intensities, as calculated by MaxQuant) between both replicates was calculated and plotted in a histogram.

3. Supplemental Figure S3 : Distribution of mouse specific proteins obtained by SILAC analysis shown in Figure 3B (mouse/human). Proteins with at least one human specific peptide (dark blue), proteins with at least one mouse specific peptide (red) protein without any identified specific human or mouse peptide (light blue) are shown.

4. Supplemental Figure S4 : HIF1  level and signaling in SW620 cells in culture and in xenograft tumors. A. Western blot analysis of HIF1- , SRC and Tubulin levels in SW60 cells derived from normoxic (20% O 2 ) or hypoxic (2% O 2 for 24 hours) culture and from xenograft tumors as indicated. B. mRNA levels of HIF1a targets VEGF and HIF2alpha. -SRC -Tubulin -HIF1-  cells 2%0 2 20%0 2 - ++SRC:-++ tumors tumors:#1#2#3#4#5#6 220 O2 (%) : cells control tumors SRC+ tumors VEGF mRNA level (% control) tumors:#1#2#3#4#5#6 220 O2 (%) : cells control tumors SRC+ tumors VEGF mRNA level (% control) A B