Supplementary Figure 5 from A Central Role for HER3 in <i>HER2</i>-Amplified Breast Cancer: Implications for Targeted Therapy

Supplementary Figure 2 from A Central Role for HER3 in HER2-Amplified Breast Cancer: Implications for Targeted Therapy

Supplementary Legends 1-6 from A Central Role for HER3 in <i>HER2</i>-Amplified Breast Cancer: Implications for Targeted Therapy

Supplementary Figure 2 from A Central Role for HER3 in HER2-Amplified Breast Cancer: Implications for Targeted Therapy

Supplementary Figure S1. KP4-derived 3D spheroids with histopathological characteristics of micrometastases show differential sensitivity to small molecule inhibitors; Supplementary Figure S2. Cobimetinib/ponatinib co-treatment increases death of pancreatic cancer cells; Supplementary Figure S3. Cobimetinib/ponatinib co-treatment impairs tumor growth in KPP xenografts; Supplementary Table S1. List of small molecule inhibitors used in drug screen; Supplementary Table S2. Genotype with key mutations of cell lines used in this study; Supplementary Table S3. Tumor growth inhibition (%TGI) of KP4 and KPP xenografts; Supplementary Table S4. TCGA microarray data for normal and PDAC tissues

<p>Supplemental Figures S1-S11. Figure S1. AXL and GAS6 expression correlates with a mesenchymal signature. Figure S2. AXL staining in TNBC tissues samples. Figure S3. TGF-β-induced EMT is reversible, and TKI resistance upon EMT is not due to drug efflux. Figure S4. AXL inhibitor R428 suppresses GAS6-induced pAXL, downstream signaling and invasion capacity. Figure S5: Inhibition of AXL does not re-sensitize erlotinib-resistant cells. Figure S6: AXL over-expression or inhibition does not alter erlotinib sensitivity in the parental HCC827 cell line. Figure S7: Summary of Bliss scores and activity of MP-470, Erlotinib and Docetaxel (DTX) or combination treatment. Figure S8. R428 synergistically interacts with anti-mitotic agents and not with Doxorubicin or Cisplatin to reduce cell viability. Figure S9. AXL inhibition in combination with anti-mitotic agents promotes mitotic death. Figure S10. Suppression of pAKT, pS6 and pCDC2 following AXL inhibition. Figure S11: AXL knock-down increases p21 expression. Table S1. Mesenchymal PC9 cells are cross-resistant to a number of anti-cancer agents.</p>

Supplementary Figure 1 from A Central Role for HER3 in HER2-Amplified Breast Cancer: Implications for Targeted Therapy

PDF file 141K, Supplementary methods for NAD quantification and the QMSP assay. Table S1 GNE-617 IC50 and mRNA Levels of NAMPT and NAPRT1, Table S2 Cell Lines Not Rescued with 10uM NA, Table S3 Cell Lines with Low NAPRT1 Expression

Supplementary Figure 4 from A Central Role for HER3 in HER2-Amplified Breast Cancer: Implications for Targeted Therapy

Supplementary Data from Oncogenic Activating Mutations Are Associated with Local Copy Gain

Abstract Although activating mutations and gains in copy number are key mechanisms for oncogene activation, the relationship between the two is not well understood. In this study, we focused on KRAS copy gains and mutations in non–small cell lung cancer. We found that KRAS copy gains occur more frequently in tumors with KRAS activating mutations and are associated with large increases in KRAS expression. These copy gains tend to be more focal in tumors with activating mutations than in those with wild-type KRAS. Fluorescence in situ hybridization analysis revealed that some tumors have homogeneous low-level gains of the KRAS locus, whereas others have high-level amplification of KRAS, often in only a fraction of tumor cells. Associations between activating mutation and copy gains were also observed for other oncogenes (EGFR in non–small cell lung cancer, BRAF and NRAS in melanoma). Activating mutations were associated with copy gains only at the mutated oncogene locus but not other oncogene loci. However, KRAS activating mutations in colorectal cancer were not associated with copy gains. Future work is warranted to clarify the relationship among the different mechanisms of oncogene activation. (Mol Cancer Res 2009;7(8):1244–52)

Supplementary Figure 1 from A Central Role for HER3 in <i>HER2</i>-Amplified Breast Cancer: Implications for Targeted Therapy

PDF file 122K, A) Chemical structure of GNE-617, B) cellular NAD and ATP levels in H522 cells after exposure to 4nM GNE-617, C) correlation of NAPRT1 mRNA and protein (n=32, spearman r= 0.88, p,0.0001)

Supplemental Dataset 1. Expression of AXL, GAS6, Vimentin and E-Cadherin in 644 human cancer cell line using RNAseq technology.

Supplementary Figure 6 from A Central Role for HER3 in HER2-Amplified Breast Cancer: Implications for Targeted Therapy

Supplementary Figure 4 from A Central Role for HER3 in <i>HER2</i>-Amplified Breast Cancer: Implications for Targeted Therapy

<p>Timelapse movie of HeLa cells treated with docetaxel (3nM) in combination with R428 (1μM).</p>

Supplementary Figure 5 from A Central Role for HER3 in HER2-Amplified Breast Cancer: Implications for Targeted Therapy

<p>Supplemental Dataset 2. Kinome profile with 1000nM R428</p>

Timelapse movie of HeLa cells treated with R428 (1μM).