Aldehyde Dehydrogenase Is Regulated by β-Catenin/TCF and Promotes Radioresistance in Prostate Cancer Progenitor Cells

Abstract

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

Cuprous oxide nanoparticles inhibit prostate cancer by attenuating the stemness of cancer cells via inhibition of the Wnt signaling pathway

“…[28][29][30] The Wnt signaling pathway is one of the important signaling pathways for maintaining stemness. 31,32 Therefore, we tried to determine whether CONPs can influence Wnt signaling. Western blot and qRT-PCR results indicated that CONPs can inhibit the expression of genes involved in Wnt signaling such as Wnt1A, FZD7, c-Myc, and Cyclin-D1, which can explain why CONPs can attenuate the stemness of prostate cancer cells and cause cell cycle arrest.…”

Aldehyde dehydrogenases in cancer stem cells: potential as therapeutic targets

“…Many ALDHs have been implicated in stem cell regulation where ALDH-dependent RA signaling is involved in gene expression and morphogenesis and is crucial for normal development ( Figure 2) (6,(12)(13)(14). In a recent study which is the focus of this perspective, Cojoc et al (15) examined the regulation of ALDH in prostate cancer stem cells (PCSCs) and its role in prostate tumor radioresistance. One of the major factors contributing to prostate cancer patient mortality is relapse following radiotherapy (16); therefore, it is crucial to identify the mechanisms that surviving cells, presumably CSCs, utilize to evade this lethal treatment and reestablish the tumor.…”

“…In order to identify genes expressed in tumor PCSCs, these cells were enriched for and isolated from a mouse xenograft tumor and genome expression analyzed (15). These cells showed a correlation between CD44+/CD133+ PCSCs and levels of ALDH1A1, ALDH3A1, ALDH3B1, and ALDH6A1; with ALDH1A1 and ALDH6A1 also being significantly enriched in prostate carcinomas compared to normal prostate tissue.…”

“…In order to examine the relation between ALDH and irradiation, prostate cancer cell lines and primary prostate tumor cells were exposed to varying doses of X-rays (15). There was a dose-dependent increase in ALDH activity and expression of CSC markers and β-catenin in the cancer cells but not in normal, immortalized prostate epithelial cell line (RWPE-1).…”

“…It appears, however, that enhanced DNA repair may only be part of the story. Radioresistant prostate cancer cells had lower baseline ROS, and ALDH+-derived xenograft tumor cells had high ALDH1A1 levels and low ROS production (15). ROS production is stimulated by irradiation and causes DNA damage (29)(30)(31).…”