APC downregulated 1 inhibits breast cancer cell invasion by inhibiting the canonical WNT signaling pathway

Cho, Sung‐Gook

doi:10.3892/ol.2017.6801

Cited by 16 publications

(17 citation statements)

References 29 publications

(39 reference statements)

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“…The function and relative regulatory mechanisms of miR-663b in CRC tumorigenesis were additionally investigated, and the results demonstrated that ectopic miR-663b expression promoted cell proliferation, migration and invasion, and decreased apoptosis in vitro. It was demonstrated that dysregulation of APC serves important role in breast cancer cell invasion through WNT signaling pathway (31). The present study revealed that the overexpression of microRNA-663b promotes CRC cell invasion.…”

Section: Discussionsupporting

confidence: 56%

MicroRNA‑663b enhances migration and invasion by targeting adenomatous polyposis coli 2 in colorectal carcinoma cells

Xiao

Chen

et al. 2020

Oncol Lett

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Colorectal carcinoma (CRC) is one of the leading causes of cancer-associated mortality worldwide. Dysregulation of microRNA (miR)-663b has been reported in a variety of diseases. However, the specific biological function of miR-663b in CRC requires further investigation. The aim of the present study was to elucidate the role and underlying molecular mechanism of action of miR-663b in CRC. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analysis and western blot analysis were employed to measure the expression of miR-663b at the RNA and protein level, respectively. Flow cytometry was used to detect cell apoptosis. Cell proliferation, migration and invasion were evaluated by the Cell Counting Kit-8, wound healing and Transwell assays, respectively. A dual-luciferase reporter assay was used to validate the potential target gene of miR-663b. The expression of miR-663b was identified to be markedly upregulated in CRC cells. Ectopic miR-663b expression promoted CRC cell proliferation, migration and invasion, and inhibited apoptosis. The dual-luciferase reporter assay identified adenomatous polyposis coli 2 (APC2) as a direct target of miR-663b in CRC cells. Further investigation indicated that miR-663b was involved in CRC cell invasion through the Wnt/β-catenin pathway. Therefore, overexpression of miR-663b was able to promote CRC cell proliferation, migration and invasion by regulating the Wnt/β-catenin pathway through targeting APC2, suggesting that miR-663b may be a useful target for the diagnosis and treatment of CRC.

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Section: Discussionsupporting

confidence: 56%

MicroRNA‑663b enhances migration and invasion by targeting adenomatous polyposis coli 2 in colorectal carcinoma cells

Xiao

Chen

et al. 2020

Oncol Lett

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“…When activated, this leads to a subsequent rise in β-catenin levels which precipitates its translocation into the nucleus to interact with transcription factors [T-cell factor (TCF) and lymphoid enhancer factor (LEF)] to promote cell proliferation and tumorigenesis (103). Both KOs also displayed reduced expression of APC down-regulated 1 (APCDD1), which also binds to WNT3a/LRP5 (102,104) and inhibits WNT/β-catenin LEF transcriptional signaling (105,106). The attenuation of negative WNT controls (APCDD1 and DKK4) in glycolytic KOs would, in theory, lead to a rise in β-catenin, which, if occurring in the cytoplasm, could interact with cadherin, bind to the actin filaments or TGF-β and alter cell-cell adhesion, thus resulting in a very loose mesenchymal phenotype contributing to metastasis.…”

Section: Reduction In Aldehyde Dehydrogenase Transcripts (Aldhs)mentioning

confidence: 99%

Whole-transcriptome Analysis of Fully Viable Energy Efficient Glycolytic-null Cancer Cells Established by Double Genetic Knockout of Lactate Dehydrogenase A/B or Glucose-6-Phosphate Isomerase

Mazzio

Badisa

Mack

et al. 2020

Cancer Genomics Proteomics

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Background/Aim: Nearly all mammalian tumors of diverse tissues are believed to be dependent on fermentative glycolysis, marked by elevated production of lactic acid and expression of glycolytic enzymes, most notably lactic acid dehydrogenase (LDH). Therefore, there has been significant interest in developing chemotherapy drugs that selectively target various isoforms of the LDH enzyme. However, considerable questions remain as to the consequences of biological ablation of LDH or upstream targeting of the glycolytic pathway. Materials and Methods: In this study, we explore the biochemical and whole transcriptomic effects of CRISPR-Cas9 gene knockout (KO) of lactate dehydrogenases A and B [LDHA/B double KO (DKO)] and glucose-6-phosphate isomerase (GPI KO) in the human colon cancer cell line LS174T, using Affymetrix 2.1 ST arrays. Results: The metabolic biochemical profiles corroborate that relative to wild type (WT), LDHA/B DKO produced no lactic acid, (GPI KO) produced minimal lactic acid and both KOs displayed higher mitochondrial respiration, and minimal use of glucose with no loss of cell viability. These findings show a high biochemical energy efficiency as measured by ATP in glycolysis-null cells. Next, transcriptomic analysis conducted on 48,226 mRNA transcripts reflect 273 differentially expressed genes (DEGS) in the GPI KO clone set, 193 DEGS in the LDHA/B DKO clone set with 47 DEGs common to both KO clones. Glycolytic-null cells reflect up-regulation in gene transcripts typically associated with nutrient deprivation / fasting and possible use of fats for energy: thioredoxin interacting protein (TXNIP), mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase 2 (HMGCS2), PPARγ coactivator 1α (PGC-1α), and acetyl-CoA acyltransferase 2 (ACAA2). Other changes in non-ergometric transcripts in both KOs show losses in "stemness", WNT signaling pathway, chemo/radiation resistance, retinoic acid synthesis, drug detoxification, androgen/estrogen activation, and extracellular matrix reprogramming genes. Conclusion: These findings demonstrate that: 1) The "Warburg effect" is dispensable, 2) loss of the LDHAB gene is not only inconsequential to viability but fosters greater mitochondrial energy, and 3) drugs that target LDHA/B are likely to be ineffective without a plausible combination second drug target. Common features across diverse mammalian tumors include the rapid glycolytic activity, greater expression of lactate dehydrogenases (LDH) and subsequent overproduction of lactic acid, occurring regardless of the presence of oxygen (Warburg effect) (1,2). This unique trait of cancer has been studied for decades, where researchers have geared off original focus from its role in metabolism to its role in acidification of the tumor microenvironment (TME), a formidable driving force for tumor growth, metastasis, aggressiveness, chemo/radiation resistance and loss of immune surveillance (3-8). This loss of immune surveillance 469 This article is freely accessible online.

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“…Aberrant regulation of Wnt/β-catenin signaling is observed in colon, ovarian, lung, prostate, liver, breast, and gastric cancers [12,[16][17][18][19][20][21]. Wnt/β-catenin signaling mediates the epithelial-tomesenchymal transition in gastric cancer [22], a process whereby epithelial cells are converted into migratory and invasive cells [23,24].…”

Section: Discussionmentioning

confidence: 99%

RNF43 and PWWP2B inhibit cancer cell proliferation and are a treatment biomarker of gastric cancer patients and their response to FDA-approved drugs

Sohn

Sul

Kim

et al. 2020

Preprint

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Background: Abnormal regulation of genes was closely related to gastric cancer. The characterization of gastric cancer has necessitated the development of new therapeutics as well as the identification of prognostic markers to predict the response to novel drugs. Methods: In our study, we have performed RNA sequencing analysis on gastric cancer tissues that decreased levels of RNF43 and PWWP2B were significantly associated with recurrence. RNF43 inhibit gastric cancer-related Wnt/β-catenin signaling by interacting with Wnt receptors. PWWP2B is unknown gene which is downregulated in gastric cancer. Therefore, we investigated the screening of 1,449 FDA-approved drugs in male-derived human cell lines such as HAP1, HAP1 RNF43 KO, and HAP1 PWWP2B KO and female-derived human cell line such as SNU620 cells. Results: We demonstrated that RNF43 KO and PWWP2B KO cells showed significantly increased proliferation and migration abilities. Next, we investigated the inhibitory effects of 1,449 drugs in HAP1, HAP1 RNF43 KO, HAP1 PWWP2B KO, and SNU620 cells. After the first round of screening, candidate drugs were selected based on an inhibition rate of > 60% loss of viability compared to wild type cells. Among these FDA-approved drugs, nine drugs (aprepitant, docetaxel trihydrate, ethinyl estradiol, griseofulvin, INC280, pelitinib, pimobendan, tepotinib, and uprosertib) showed strong inhibitory effects in RNF43 KO cells and PWWP2B KO cells. Migration and apoptosis analyses demonstrated that docetaxel trihydrate and pelitinib showed the best inhibition and apoptotic rates, with the smallest half maximal inhibitory concentrations among the screened candidate drugs. In a murine xenograft model, tumor volumes were significantly reduced in the docetaxel trihydrate, uprosertib or pelitinib-treated group, when administered by oral gavage.Conclusions: Our data demonstrated that RNF43 and PWWP2B are a biomarker that predict recurrence of gastric cancer. Our findings suggest that pelitinib could be used as novel therapeutic agents for the prevention and treatment of gastric cancer with an aberrant decrease in RNF43 and PWWP2B expression.

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APC downregulated 1 inhibits breast cancer cell invasion by inhibiting the canonical WNT signaling pathway

Cited by 16 publications

References 29 publications

MicroRNA‑663b enhances migration and invasion by targeting adenomatous polyposis coli 2 in colorectal carcinoma cells

MicroRNA‑663b enhances migration and invasion by targeting adenomatous polyposis coli 2 in colorectal carcinoma cells

Whole-transcriptome Analysis of Fully Viable Energy Efficient Glycolytic-null Cancer Cells Established by Double Genetic Knockout of Lactate Dehydrogenase A/B or Glucose-6-Phosphate Isomerase

RNF43 and PWWP2B inhibit cancer cell proliferation and are a treatment biomarker of gastric cancer patients and their response to FDA-approved drugs

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