Wnt/β-catenin signaling plays an ever-expanding role in stem cell self-renewal, tumorigenesis and cancer chemoresistance

Mohammed, Maryam K.; Shao, Connie; Wang, Jing; Wei, Qiang; Wang, Xin Xin; Collier, Zachary J; Tang, Shengli; Líu, Hao; Zhang, Fugui; Huang, Jiayi; Guo, Dan; Lu, Minpeng; Liu, Feng; Liu, Jianxiang; C, Ma; Shi, Lewis L.; Athiviraham, Aravind; He, Tong‐Chuan; Lee, Michael J.

doi:10.1016/j.gendis.2015.12.004

Cited by 226 publications

(182 citation statements)

References 343 publications

(441 reference statements)

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“…The Wnt/β-catenin pathway is an evolutionarily conserved pathway, which is important in initiating and regulating a diverse range of cellular activities, including cell proliferation, calcium homeostasis and cell polarity (28). There are a number of target proteins in the Wnt/β-catenin signaling pathway, including c-Myc, cyclin D1, MMP3 and LEF.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-552 promotes tumor cell proliferation and migration by directly targeting DACH1 via the Wnt/β-catenin signaling pathway in colorectal cancer

et al. 2017

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Abstract. The purpose of the present study was to analyze the crucial role of microRNAs (miRNAs/miRs) involved in the proliferation and migration of colorectal cancer (CRC) and to investigate their underlying mechanisms. The present study discusses the expression and function of miR-552 in CRC. The expression level of miR-552 in CRC cells and tissues was observed, and it was suggested that the high expression of miR-552 accelerated the proliferation and migration of CRC cells in vitro. Notably, a result of the present study was that the cell fate determination factor Dachshund family transcription factor 1 (DACH1) was identified as a direct target of miR-552. Suppressing miR-552 expression in CRC cells increased endogenous DACH1 mRNA and protein levels, which was negatively correlated with miR-552. DACH1 performs an important role in the development of a number of neoplasms, and has the ability to regulate the Wnt/β-catenin signaling pathway as a novel predictive and diagnostic biomarker. Accordingly, it was concluded that miR-552 exerted a tumor-promoting role in CRC development by targeting DACH1, which may contribute to the increase in the rates of CRC proliferation and migration. miR-552 may serve as a potential diagnostic and prognostic biomarker for CRC. IntroductionColorectal cancer (CRC) has one of the highest cure rates of all types of malignant tumors (1), however remains ranked as the fourth leading cause of cancer-associated mortality in the world (2). In previous years, the morbidity and mortality rates of CRC have significantly increased due to an ageing population, and with changes in eating habits and lifestyles (3). The development of distant metastasis is a major cause of cancer-associated mortalities in CRC patients (4). Overwhelming evidence has demonstrated that aberrant expression of microRNA (miRNA/miR) contributes to CRC development by affecting the expression of the genes that regulate cancer progression (5).miRNAs, endogenous small non-coding regulatory RNAs measuring 18-25 nucleotides long (6), usually regulate gene expression in a number of tumor-associated signaling pathways at the post-transcriptional level, including the Wnt/β-catenin signaling pathway (7). As miRNAs tend to be localized to fragile chromosomal regions (8), they have the ability to adjust the levels of their corresponding mRNAs, and serve critical roles in the physiological and pathological processes of tumor development, which are a novel aspect of cancer studies. Previous evidence has demonstrated that miRNAs are involved in a number of biological processes, including proliferation, differentiation, migration, angiogenesis and protein splitting (9-11). miRNAs also serve as tumor promoter genes or tumor suppressor genes by negatively regulating their targets. These data suggest a possibility that miRNA is a novel focus for examining the current diagnosis and treatment of tumors.Previously, several studies revealed that miR-124 results in a decrease in the proliferation ability of CRC cells by targeting ribose-phosp...

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Section: Discussionmentioning

confidence: 99%

MicroRNA-552 promotes tumor cell proliferation and migration by directly targeting DACH1 via the Wnt/β-catenin signaling pathway in colorectal cancer

et al. 2017

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“…Thus, overexpression of sox7 in PGCs may cause ectopic expression of these endodermal differentiation genes, resulting in apoptosis of PGCs and ultimately a reduction in their number. Additionally, the Wnt/β-catenin signaling pathway has been reported to promote stem cell self-renewal and cell survival (reviewed by Mohammed et al, 2016), two characteristics necessary to preserve the germline. Xlsox7 harbors the β-cateninbinding motif DRNEFDQYL (Guo et al, 2008), suggesting that sox7 inhibition might cause reduced PGC number by influencing gene expression downstream of Wnt signaling.…”

Section: Sox7 Is Required For Pgc Developmentmentioning

confidence: 99%

High-throughput analysis reveals novel maternal germline RNAs crucial for primordial germ cell preservation and proper migration

et al. 2017

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During oogenesis, hundreds of maternal RNAs are selectively localized to the animal or vegetal pole, including determinants of somatic and germline fates. Although microarray analysis has identified localized determinants, it is not comprehensive and is limited to known transcripts. Here, we utilized high-throughput RNAsequencing analysis to comprehensively interrogate animal and vegetal pole RNAs in the fully grown Xenopus laevis oocyte. We identified 411 (198 annotated) and 27 (15 annotated) enriched mRNAs at the vegetal and animal pole, respectively. Ninety were novel mRNAs over 4-fold enriched at the vegetal pole and six were over 10-fold enriched at the animal pole. Unlike mRNAs, microRNAs were not asymmetrically distributed. Whole-mount in situ hybridization confirmed that all 17 selected mRNAs were localized. Biological function and network analysis of vegetally enriched transcripts identified protein-modifying enzymes, receptors, ligands, RNA-binding proteins, transcription factors and co-factors with five defining hubs linking 47 genes in a network. Initial functional studies of maternal vegetally localized mRNAs show that sox7 plays a novel and important role in primordial germ cell (PGC) development and that ephrinB1 (efnb1) is required for proper PGC migration. We propose potential pathways operating at the vegetal pole that highlight where future investigations might be most fruitful.

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“…4B). Wnt activation is known to be mediated by Dishevelled, which mediates the intracellular accumulation of the β-catenin protein followed by the induction of Dkk1 (Mohammed et al, 2016). To confirm the effect of ROS on Wnt activation, we examined the expression level and nuclear translocation of β-catenin.…”

Section: Nnk Induces the Wnt Pathway In A549 Cellsmentioning

confidence: 99%

Tobacco nitrosamine NNK increases ALDH-positive cells via ROS-Wnt signaling pathway in A549 human lung cancer cells

et al. 2017

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-Epidemiological studies suggest that lung cancer, which is a major cause of cancer death, has a critical association with cigarette smoking. Tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in cigarette smoke is a major risk factor for carcinogenesis. However, the mechanisms by which NNK promotes cancer development have not been fully elucidated. Growing evidence suggests that lung cancer originates from cancer stem cells (CSCs), which are a minor population of lung cancer cells. In the present study, we investigated the effects of NNK on the CSCs in A549 human lung cancer cells using flow cytometry with aldehyde dehydrogenase (ALDH), a functional marker of CSCs. We found that NNK increased the proportion of ALDH-positive cells in a dose-dependent manner. A Wnt inhibitor PNU74654 reduced NNK-induced expression levels of Wnt target gene Dkk1 and increase in ALDH-positive cells. We next examined the signaling pathway that mediates the NNKinduced increase in ALDH-positive cells via Wnt signaling. DCF assay revealed that NNK induced reactive oxygen species (ROS) production. The ROS scavenger N-acetylcysteine (NAC) inhibited the NNKinduced Wnt activation and increase in ALDH-positive cells. These data suggest that NNK-induced ROS activate the Wnt signaling pathway in A549 cells. These findings would provide new insights into the role of NNK in the lung CSCs.

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Wnt/β-catenin signaling plays an ever-expanding role in stem cell self-renewal, tumorigenesis and cancer chemoresistance

Cited by 226 publications

References 343 publications

MicroRNA-552 promotes tumor cell proliferation and migration by directly targeting DACH1 via the Wnt/β-catenin signaling pathway in colorectal cancer

MicroRNA-552 promotes tumor cell proliferation and migration by directly targeting DACH1 via the Wnt/β-catenin signaling pathway in colorectal cancer

High-throughput analysis reveals novel maternal germline RNAs crucial for primordial germ cell preservation and proper migration

Tobacco nitrosamine NNK increases ALDH-positive cells via ROS-Wnt signaling pathway in A549 human lung cancer cells

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