American Association for Cancer Research
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Supplementary Methods, Table 1, Figure S1-S9 from Aldehyde Dehydrogenase Is Regulated by β-Catenin/TCF and Promotes Radioresistance in Prostate Cancer Progenitor Cells

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posted on 2023-03-30, 23:42 authored by Monica Cojoc, Claudia Peitzsch, Ina Kurth, Franziska Trautmann, Leoni A. Kunz-Schughart, Gennady D. Telegeev, Eduard A. Stakhovsky, John R. Walker, Karl Simin, Stephen Lyle, Susanne Fuessel, Kati Erdmann, Manfred P. Wirth, Mechthild Krause, Michael Baumann, Anna Dubrovska

Supplementary Methods, Table 1, Figure S1-S9 (i) supplementary methods: Human tumor tissue dissociation, Immunofluorescence microscopy, Clonogenic cell survival assay, Sphere formation assay, Cell proliferation and cytotoxicity assay, Wound healing assay, Transwell migration assay, Western blot analysis, Flow cytometry analysis, Chromatin immunoprecipitation assay, siRNA-mediated gene silencing, Luciferase reporter assay, Histology, Microarray analysis of the xenograft tumors, (ii) supplementary table 1: Primary tumor tissues used in the study and (iii) supplementary figures including Figure S1 (analysis of ALDH1A1 expression in normal and tumor prostate tissues), Figure S2 (prostate cancer ALDH+ cells possess CSC properties), Figure S3 (analysis of CSC marker expression after irradiation), Figure S4 (clonogenicity and tumorigenisity of ALDH+ and ALDH- cells after irradiation), Figure S5 (characterization of the radioresistant prostate cancer cell sublines), Figure S6 (the mechanisms of prostate cancer cell radioresistance), Figure S7 (comparative gene expression profiling of ALDH+ and radioresistant DU145 cells), Figure S8 (EMT properties of ALDH+ and radioresistant prostate cancer cells), Figure S9 (WNT/β-catenin pathway regulates ALDH1A1 expression)



Radiotherapy is a curative treatment option in prostate cancer. Nevertheless, patients with high-risk prostate cancer are prone to relapse. Identification of the predictive biomarkers and molecular mechanisms of radioresistance bears promise to improve cancer therapies. In this study, we show that aldehyde dehydrogenase (ALDH) activity is indicative of radioresistant prostate progenitor cells with an enhanced DNA repair capacity and activation of epithelial–mesenchymal transition (EMT). Gene expression profiling of prostate cancer cells, their radioresistant derivatives, ALDH+ and ALDH− cell populations revealed the mechanisms, which link tumor progenitors to radioresistance, including activation of the WNT/β-catenin signaling pathway. We found that expression of the ALDH1A1 gene is regulated by the WNT signaling pathway and co-occurs with expression of β-catenin in prostate tumor specimens. Inhibition of the WNT pathway led to a decrease in ALDH+ tumor progenitor population and to radiosensitization of cancer cells. Taken together, our results indicate that ALDH+ cells contribute to tumor radioresistance and their molecular targeting may enhance the effectiveness of radiotherapy. Cancer Res; 75(7); 1482–94. ©2015 AACR.

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