0000000000633998

AUTHOR

Kristiaan J. Lenos

Additional file 1 of Subtype-specific kinase dependency regulates growth and metastasis of poor-prognosis mesenchymal colorectal cancer

Additional file 1: Supplementary Fig. S1. Validation of PAK2 as an essential kinase for CMS4 cell lines. A, PAK1–3 mRNA expression levels in a panel of 28 CRC cell lines, also including those used for the drop-out screen, as determined by quantitative PCR. Of note: diamond for PAK3 located on x-axis indicates no mRNA could be detected in this sample. B, C, 2Log mRNA expression levels of PAK4–6 in CRC cell lines (B) and tumors (C), determined by microarray or RNA sequencing. D, Western blot for PAK1 protein expression in HT55 & SW948 (CMS2) and HuTu-80 & MDST8 (CMS4). 2,2,2-Trichloroethanol (2,2,2TCE) signal (excerpt taken around 60 kDa region) indicates amount of protein loaded per …

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Subtype-specific kinase dependency regulates growth and metastasis of poor-prognosis mesenchymal colorectal cancer

Abstract Background Colorectal cancer (CRC) can be divided into four consensus molecular subtypes (CMS), each with distinct biological features. CMS4 is associated with epithelial-mesenchymal transition and stromal infiltration (Guinney et al., Nat Med 21:1350–6, 2015; Linnekamp et al., Cell Death Differ 25:616–33, 2018), whereas clinically it is characterized by lower responses to adjuvant therapy, higher incidence of metastatic spreading and hence dismal prognosis (Buikhuisen et al., Oncogenesis 9:66, 2020). Methods To understand the biology of the mesenchymal subtype and unveil specific vulnerabilities, a large CRISPR-Cas9 drop-out screen was performed on 14 subtyped CRC cell lines to un…

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Additional file 10 of Subtype-specific kinase dependency regulates growth and metastasis of poor-prognosis mesenchymal colorectal cancer

Additional file 10. Full Western blot membrane images represented in the manuscript.

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Stem cell functionality is microenvironmentally defined during tumour expansion and therapy response in colon cancer

Solid malignancies have been speculated to depend on cancer stem cells (CSCs) for expansion and relapse after therapy. Here we report on quantitative analyses of lineage tracing data from primary colon cancer xenograft tissue to assess CSC functionality in a human solid malignancy. The temporally obtained clone size distribution data support a model in which stem cell function in established cancers is not intrinsically, but is entirely spatiotemporally orchestrated. Functional stem cells that drive tumour expansion predominantly reside at the tumour edge, close to cancer-associated fibroblasts. Hence, stem cell properties change in time depending on the cell location. Furthermore, although…

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Additional file 8 of Subtype-specific kinase dependency regulates growth and metastasis of poor-prognosis mesenchymal colorectal cancer

Additional file 8: Table S1. Raw normalized sgRNA counts per sample per cell line of the CRISPR-Cas9 drop-out screen performed.

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Additional file 9 of Subtype-specific kinase dependency regulates growth and metastasis of poor-prognosis mesenchymal colorectal cancer

Additional file 9: Table S2. Results from analysis of CRISPR-Cas9 drop-out screen representing the fold change within each replicate of sgRNA counts between t1 and t0.

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