Dataset Information

CCAAT-displacement protein/cut homeobox transcription factor (CUX1) represses estrogen receptor-alpha (ER-?) in triple-negative breast cancer cells and can be antagonized by muscadine grape skin extract (MSKE).

ABSTRACT: Triple-Negative Breast Cancers (TNBCs) are the most difficult to treat subtype of breast cancer and are often associated with high nuclear expression of Snail and Cathepsin L (Cat L) protease. We have previously shown that Snail can increase Cat L expression/activity in prostate and breast cancer cells. This study investigated the role of CUX1 (a downstream substrate of Cat L) in TNBC. We showed that Cat L and CUX1 were highly expressed in TNBC patient tissue/cell lines, as compared to ER-positive samples, using cBioportal data and western blot/zymography analyses. Additionally, luciferase reporter and chromatin immunoprecipitation assays showed that CUX1 directly bound to estrogen receptor-alpha (ER-?) promoter in MDA-MB-468, a representative TNBC cell line, and that CUX1 siRNA could restore ER-? transcription and protein expression. Furthermore, Snail and CUX1 expression in various TNBC cell lines was inhibited by muscadine grape skin extract (MSKE, a natural grape product rich in anthocyanins) or Cat L inhibitor (Z-FY-CHO) leading to decreased cell invasion and migration. MSKE decreased cell viability and increased expression of apoptotic markers in MDA-MB-468 cells, with no effect on non-tumorigenic MCF10A cells. MSKE also decreased CUX1 binding to ER-? promoter and restored ER-? expression in TNBC cells, while both MSKE and CUX1 siRNA restored sensitivity to estradiol and 4-hydoxytamoxifen as shown by increased cell viability. Therefore, CUX1 activated by Snail-Cat L signaling may contribute to TNBC via ER-? repression, and may be a viable target for TNBC using natural products such as MSKE that targets cancer and not normal cells.

SUBMITTER: Burton LJ

PROVIDER: S-EPMC6460785 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Publications

CCAAT-displacement protein/cut homeobox transcription factor (CUX1) represses estrogen receptor-alpha (ER-α) in triple-negative breast cancer cells and can be antagonized by muscadine grape skin extract (MSKE).

Burton Liza J LJ Hawsawi Ohuod O Sweeney Janae J Bowen Nathan N Hudson Tamaro T Odero-Marah Valerie V

PloS one 20190409 4

Triple-Negative Breast Cancers (TNBCs) are the most difficult to treat subtype of breast cancer and are often associated with high nuclear expression of Snail and Cathepsin L (Cat L) protease. We have previously shown that Snail can increase Cat L expression/activity in prostate and breast cancer cells. This study investigated the role of CUX1 (a downstream substrate of Cat L) in TNBC. We showed that Cat L and CUX1 were highly expressed in TNBC patient tissue/cell lines, as compared to ER-positi ...[more]

PMID: 30964885

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Project description:In this study, biometrics assessment of flower structure, cluster-, and berry-related traits were evaluated in a population of 90 muscadine grape genotypes for three consecutive years. This population consisted of 21 standard cultivars, 60 breeding lines, and 9 Vitis x Muscadinia hybrids (VM hybrids). Cluster length (CL) and width (CWI) characteristics exhibited slight differences among the population, with a range estimated at 7.1 and 4.6 cm, respectively. However, cluster weight (CWE), number of berries/cluster (N.B/C), and cluster compactness (CC) traits showed more diversity between individuals with a calculated range of 205.6 g, 32.6 B/C, and 24.1, respectively. Interestingly, all berry-related traits greatly varied between individuals, excluding the number of seeds/berry (N.S/B) character. The N.S/B trait displayed a narrow range of 5.6 seeds within the population. However, characters of berry length (BL), width (BWI), weight (BWE), the weight of seeds/berry (W.S/B), firmness (FF), and dry scar pattern (SP) demonstrated a wide estimated range of 21.2 mm, 21.7 mm, 25.4 g, 0.71 g, 0.21 N, and 82%, respectively. Normal distribution analysis for each trait suggested different distribution patterns extended between unimodal to multimodal behavior. Hierarchical mapping analysis was able to classify the population into several clades based on physical cluster- and berry-related attributes. The PCA suggested that hermaphroditic (perfect) flower structure is associated with compact clusters exhibiting small berries in size and weight (i.e., muscadine genotypes suitable for wine production). However, female flower structure is associated with clusters displaying large berries in size and weight (i.e., muscadine genotypes appropriate for fresh consumption). These patterns occurred independently of cluster size and weight characters. This research is the first study evaluating muscadine biometrics characters at a population level, providing valuable information for market demand and muscadine breeding programs.

Dataset Information

CCAAT-displacement protein/cut homeobox transcription factor (CUX1) represses estrogen receptor-alpha (ER-?) in triple-negative breast cancer cells and can be antagonized by muscadine grape skin extract (MSKE).

Publications

CCAAT-displacement protein/cut homeobox transcription factor (CUX1) represses estrogen receptor-alpha (ER-α) in triple-negative breast cancer cells and can be antagonized by muscadine grape skin extract (MSKE).

Similar Datasets

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