Table 1.

Proteins altered by ABT-263-crizotinib as assessed by RPPA. TNBC cell lines were exposed to 1μM crizotinib or 1μM ABT-263 alone or their combination in duplicate for 24h, and the protein extracts were assayed for the expression of basal and activated levels of 291 proteins at the RPPA Core Facility at the MD Anderson Cancer Center (Houston, TX). Top altered proteins are listed and their fold change compared with respective vehicle treated controls is shown in brackets. Blue indicates proteins upregulated while red indicates proteins downregulated by the drug combination. Interesting candidate proteins are represented in bold.

Crizotinib (Protein FC relative to control)	ABT-263 (Protein FC relative to control)	Combination (Protein FC relative to control)
HCC38
DM Histone H3 (1.11) Histone H3 (1.18) PAI1 (1.19) PAR (1.01) Collagen IV (1.3) Cleaved Caspase-7 (1.03) Cleaved Caspase-3 (1.04) p27 Kip1 (1.03) Bcl-xL (0.99) p44/42 MAPK (0.99) p38 p180_pY182 (0.95) LDHA (1.04)	DM Histone H3 (2.09) Histone H3 (2.26) PAI1 (1.45) PAR (4.35) Collagen IV (1.86) Cleaved Caspase-7 (1.58) Cleaved Caspase-3 (1.23) p27 Kip1 (1.03) Bcl-xL (0.91) p44/42 MAPK (0.85) p38 p180_pY182 (0.65) LDHA (0.47)	$\text{DM Histone H}3\left(6.62\right)$ $\text{Histone H}3\left(4.81\right)$ $\text{PAI}1\left(1.64\right)$ $\mathbf{PAR}\left(\mathbf{5.93}\right)$ $\text{Collagen IV}\left(1.88\right)$ $\mathbf{Cleaved}\mathbf{Caspase}\mathbf{-}\mathbf{7}\left(\mathbf{1.74}\right)$ $\mathbf{Cleaved}\mathbf{Caspase}\mathbf{-}\mathbf{3}\left(\mathbf{1.39}\right)$ $\mathrm{p}27\text{ Kip}1\left(1.18\right)$ $\text{Bcl-xL}\left(0.91\right)$ $\mathbf{p}\mathbf{44}/\mathbf{42}\mathbf{M}\mathbf{A}\mathbf{P}\mathbf{K}\left(\mathbf{0.77}\right)$ $\mathbf{p}\mathbf{38}\mathbf{p}\mathbf{180}\_\mathbf{p}\mathbf{Y}\mathbf{182}\left(\mathbf{0.67}\right)$ $\mathbf{L}\mathbf{D}\mathbf{H}\mathbf{A}\left(\mathbf{0.51}\right)$
MDA-MB-468
PAI1 (1.41) PAR (1.29) Collagen IV (1.05) NDRG1_pT346 (1.55) Bcl-xL (1.06) MAPK_pT202_Y204 (0.91) EGFR_pY1068 (0.84) LDHA (1.05) B7H4 (0.83) X14.3.3.zeta (0.77)	PAI1 (1.45) PAR (1.33) Collagen IV (1.08) NDRG1_pT346 (1.54) Bcl-xL (0.91) MAPK_pT202_Y204 (0.82) EGFR_pY1068 (0.92) LDHA (0.79) B7H4 (0.92) X14.3.3.zeta (0.98)	$\text{PAI}1\left(1.58\right)$ $\mathbf{P}\mathbf{A}\mathbf{R}\left(\mathbf{1.39}\right)$ $\text{Collagen IV}\left(1.29\right)$ $\text{NDRG}1\_\text{pT}346\left(1.57\right)$ $\text{Bcl-xL}\left(0.88\right)$ $\mathbf{M}\mathbf{A}\mathbf{P}\mathbf{K}\_\mathbf{p}\mathbf{T}\mathbf{202}\_\mathbf{Y}\mathbf{204}\left(\mathbf{0.80}\right)$ $\text{EGFR\_pY}1068\left(0.87\right)$ $\mathbf{L}\mathbf{D}\mathbf{H}\mathbf{A}\left(\mathbf{0}.\mathbf{78}\right)$ $\mathrm{B}7\mathrm{H}4\left(0.87\right)$ $\mathrm{X}\mathrm{14.3.3.}\text{zeta}\left(0.83\right)$
MDA-MB-231
Collagen IV (1.16) PAR (1.05) S6_pS235_S236 (0.95) S6_pS240_S244 (0.87) Bcl-xL (0.95) LDHA (0.95) B7H4 (0.94) Bad_pS112 (0.97)	Collagen IV (1.11) PAR (1.21) S6_pS235_S236 (0.75) S6_pS240_S244 (0.73) Bcl-xL (0.82) LDHA (0.73) B7H4 (0.77) Bad_pS112 (0.88)	$\text{Collagen IV}\left(1.33\right)$ $\mathbf{P}\mathbf{A}\mathbf{R}\left(\mathbf{1}.\mathbf{15}\right)$ $\mathbf{S}\mathbf{6}\_\mathbf{p}\mathbf{S}\mathbf{235}\_\mathbf{S}\mathbf{236}\left(\mathbf{0}.\mathbf{73}\right)$ $\mathbf{S}\mathbf{6}\_\mathbf{p}\mathbf{S}\mathbf{240}\_\mathbf{S}\mathbf{244}\left(\mathbf{0}.\mathbf{76}\right)$ $\text{Bcl-xL}\left(0.91\right)$ $\mathbf{L}\mathbf{D}\mathbf{H}\mathbf{A}\left(\mathbf{0}.\mathbf{83}\right)$ $\mathrm{B}7\mathrm{H}4\left(0.75\right)$ $\text{Bad\_pS}112\left(0.89\right)$
BT-20
DM Histone H3 (1.04) Histone H3 (0.98) Collagen IV (1.07) PAR (1.08) Mcl1 (1.00) PDL1 (1.02) p21 (0.95) Bcl-xL (1.00) LDHA (1.10) SDHA (0.99) NDRG1_pT346 (0.98) MAPK_pT202_Y204 (1.18)	DM Histone H3 (1.63) Histone H3 (1.67) Collagen IV (1.07) PAR (3.34) Mcl1 (1.74) PDL1 (1.70) p21 (1.28) Bcl-xL (0.78) LDHA (0.64) SDHA (0.54) NDRG1_pT346 (0.56) MAPK_pT202_Y204 (0.67)	$\text{DM Histone H}3\left(1.82\right)$ $\text{Histone H}3\left(1.65\right)$ $\text{Collagen IV}\left(1.59\right)$ $\mathbf{P}\mathbf{A}\mathbf{R}\left(\mathbf{2}.\mathbf{91}\right)$ $\text{Mcl}1\left(1.74\right)$ $\text{PDL}1\left(1.64\right)$ $\mathrm{p}21\left(1.2\right)$ $\text{Bcl-xL}\left(0.81\right)$ $\mathbf{L}\mathbf{D}\mathbf{H}\mathbf{A}\left(\mathbf{0}.\mathbf{55}\right)$ $\text{SDHA}\left(0.57\right)$ $\text{NDRG}1\text{\_pT}346\left(0.60\right)$ $\mathbf{M}\mathbf{A}\mathbf{P}\mathbf{K}\_\mathbf{p}\mathbf{T}\mathbf{202}\_\mathbf{Y}\mathbf{204}\left(\mathbf{0}.\mathbf{62}\right)$
BT-549
DM Histone H3 (1.23) Histone H3 (1.28) Mcl-1 (1.31) PAR (1.39) S6_pS235_S236 (0.95) S6_pS240_S244 (0.92) Bcl-xL (1.00) LDHA (0.688)	DM Histone H3 (1.05) Histone H3 (1.28) Mcl-1 (1.31) PAR (1.39) S6_pS235_S236 (1.23) S6_pS240_S244 (1.08) Bcl-xL (0.92) LDHA (0.688)	$\text{DM Histone H}3\left(1.23\right)$ $\text{Histone H}3\left(1.28\right)$ $\text{Mcl-}1\left(1.31\right)$ $\text{PAR}\left(1.39\right)$ $\mathrm{S}6\text{\_pS}235\_\mathrm{S}236\left(1.18\right)$ $\mathrm{S}6\text{\_pS}240\text{\_S}244\left(1.13\right)$ $\text{Bcl-xL}\left(0.95\right)$ $\text{LDHA}\left(0.68\right)$
MDA-MB-436
Mcl1 (1.10) DUSP4 (0.99) Histone H3 (1.01) DM Histone H3 (1.04) PAI1 (1.09) PAR (0.91) Collagen IV (0.96) Bcl-xL (0.97)	Mcl1 (1.46) DUSP4 (1.45) Histone H3 (1.36) DM Histone H3 (1.33) PAI1 (1.20) PAR (1.34) Collagen IV (1.07) Bcl-xL (1.04)	$\text{Mcl}1\left(1.50\right)$ $\text{DUSP}4\left(1.433\right)$ $\text{Histone H}3\left(1.28\right)$ $\text{DM Histone H}3\left(1.23\right)$ $\text{PAI}1\left(1.23\right)$ $\text{PAR}\left(1.20\right)$ $\text{Collagen IV}\left(1.1\right)$ $\text{Bcl-xL}\left(0.97\right)$