Supplementary Tables, Materials and Methods from ADNP Is a Therapeutically Inducible Repressor of WNT Signaling in Colorectal Cancer

Blaj, Cristina; Bringmann, Agnes; Schmidt, Eva Marina; Urbischek, Manuela; Lamprecht, Sebastian; Fröhlich, Thomas; Arnold, Georg J.; Krebs, Stefan; Blum, Helmut; Hermeking, Heiko; Jung, Andreas; Kirchner, Thomas; Horst, David

doi:10.1158/1078-0432.22462845.v1

Supplementary Tables, Materials and Methods from ADNP Is a Therapeutically Inducible Repressor of WNT Signaling in Colorectal Cancer

https://doi.org/10.1158/1078-0432.22462845

journal contribution

posted on 2023-03-31, 19:26 authored by Cristina Blaj, Agnes Bringmann, Eva Marina Schmidt, Manuela Urbischek, Sebastian Lamprecht, Thomas Fröhlich, Georg J. Arnold, Stefan Krebs, Helmut Blum, Heiko Hermeking, Andreas Jung, Thomas Kirchner, David Horst

<p>Supplementary Tables 1-7 Supplementary Materials and Methods Suppl. Table 1. WNT target gene sets used for GSEA Suppl. Table 2. Gene Expression (real-time RT-PCR) primers used in this study. Primers were selected from the Universal Probe Library (Roche). Suppl. Table 3. Antibodies used for immunoblotting and immunohistochemistry. Suppl. Table 4. Fold change (F.C.) of consistently deregulated genes in three gene expression data sets of colon cancer cells with high vs. low WNT activity, and F.C. in differential expression of these genes in TCGA data in colon cancer vs. normal mucosa. P values are t test results. Suppl. Table 5. Proteome analysis results upon ADNP depletion. Proteins with significant up- or downregulation are listed (P < 0.05; abs. fold change >1.5) Suppl. Table 6. Clinical/pathological data and ADNP expression in colorectal cancer. Suppl. Table 7. Multivariate analysis of cancer specific survival.</p>

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Deutsche Forschungsgemeinschaft

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DOI - Is supplement to ADNP Is a Therapeutically Inducible Repressor of WNT Signaling in Colorectal Cancer

ARTICLE ABSTRACT

Purpose: Constitutively active WNT signaling is a hallmark of colorectal cancers and a driver of malignant tumor progression. Therapeutic targeting of WNT signaling is difficult due to high pathway complexity and its role in tissue homeostasis. Here, we identify the transcription factor ADNP as a pharmacologically inducible repressor of WNT signaling in colon cancer.Experimental Design: We used transcriptomic, proteomic, and in situ analyses to identify ADNP expression in colorectal cancer and cell biology approaches to determine its function. We induced ADNP expression in colon cancer xenografts by low-dose ketamine in vivo. Clinical associations were determined in a cohort of 221 human colorectal cancer cases.Results: ADNP was overexpressed in colon cancer cells with high WNT activity, where it acted as a WNT repressor. Silencing ADNP expression increased migration, invasion, and proliferation of colon cancer cells and accelerated tumor growth in xenografts in vivo. Treatment with subnarcotic doses of ketamine induced ADNP expression, significantly inhibited tumor growth, and prolonged survival of tumor-bearing animals. In human patients with colon cancer, high ADNP expression was linked to good prognosis.Conclusions: Our findings indicate that ADNP is a tumor suppressor and promising prognostic marker, and that ketamine treatment with ADNP induction is a potential therapeutic approach that may add benefit to current treatment protocols for patients with colorectal cancer. Clin Cancer Res; 23(11); 2769–80. ©2016 AACR.