BHX Inhibits the Wnt Signaling Pathway by Suppressing β-catenin Transcription in the Nucleus

Ding, Fengxia; Wang, Meisa; Du, Yibo; Du, Shuangshuang; Zhu, Zhongling; Zhao, Yan

doi:10.1038/srep38331

Cited by 8 publications

(5 citation statements)

References 36 publications

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“…Validating our hypothesis that CDH11 may promote β-catenin nuclear translocation and WNT activation, we demonstrated that CDH11 modulates β-catenin expression levels and that CDH11/β-catenin signalling axis plays a regulatory role for the canonical WNT signalling pathway in TNBC (Figure 3), as concomitant decreased CDH11 and β-catenin in the TNBC cell was observed, with siCDH11 cells exhibiting reduced CDH11/β-catenin nuclear co-localization compared to the control WT cells (Figure 4). This is consistent with studies suggesting that the transcriptional suppression of β-catenin was associated with inhibition of the WNT signalling activity in MCF-4 and A549 cell lines [31]. Based on our immunofluorescence and IHC staining, CDH11 localizes in the membrane and cytoplasm.…”

Section: Discussionsupporting

confidence: 92%

Cadherin 11 Inhibition Downregulates β-catenin, Deactivates the Canonical WNT Signalling Pathway and Suppresses the Cancer Stem Cell-Like Phenotype of Triple Negative Breast Cancer

Satriyo

Bamodu

Chen

et al. 2019

JCM

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Background: Cancer stem cells (CSCs) promote tumor progression and distant metastasis in breast cancer. Cadherin 11 (CDH11) is overexpressed in invasive breast cancer cells and implicated in distant bone metastases in several cancers. The WNT signalling pathway regulates CSC activity. Growing evidence suggest that cadherins play critical roles in WNT signalling pathway. However, CDH11 role in canonical WNT signalling and CSCs in breast cancer is poorly understood. Methods: We investigated the functional association between CDH11 and WNT signalling pathway in triple negative breast cancer (TNBC), by analyzing their expression profile in the TCGA Breast Cancer (BRCA) cohort and immunohistochemical (IHC) staining of TNBC samples. Results: We observed a significant correlation between high CDH11 expression and poor prognosis in the basal and TNBC subtypes. Also, CDH11 expression positively correlated with β-catenin, wingless type MMTV integration site (WNT)2, and transcription factor (TCF)12 expression. IHC results showed CDH11 and β-catenin expression significantly correlated in TNBC patients (p < 0.05). We also showed that siRNA-mediated loss-of-CDH11 (siCDH11) function decreases β-catenin, Met, c-Myc, and matrix metalloproteinase (MMP)7 expression level in MDA-MB-231 and Hs578t. Interestingly, immunofluorescence staining showed that siCDH11 reduced β-catenin nuclear localization and attenuated TNBC cell migration, invasion and tumorsphere-formation. Of translational relevance, siCDH11 exhibited significant anticancer efficacy in murine tumor xenograft models, as demonstrated by reduced tumor-size, inhibited tumor growth and longer survival time. Conclusions: Our findings indicate that by modulating β-catenin, CDH11 regulates the canonical WNT signalling pathway. CDH11 inhibition suppresses the CSC-like phenotypes and tumor growth of TNBC cells and represents a novel therapeutic approach in TNBC treatment.

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Section: Discussionsupporting

confidence: 92%

Cadherin 11 Inhibition Downregulates β-catenin, Deactivates the Canonical WNT Signalling Pathway and Suppresses the Cancer Stem Cell-Like Phenotype of Triple Negative Breast Cancer

Satriyo

Bamodu

Chen

et al. 2019

JCM

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“…In the treatment group, H460 cells were implanted in BALB/c (nude) mice via subcutaneous injection. For the positive control, BALB/c (nude) mice were injected with cisplatin [23]. Growth of the implanted tumors was significantly inhibited in the cisplatin group; however, the body weights of the cisplatin-mice decreased rapidly.…”

Section: Sfp Inhibits the Proliferation Of Lung Cancer Cells In Vitromentioning

confidence: 99%

Silk fibroin peptide suppresses proliferation and induces apoptosis and cell cycle arrest in human lung cancer cells

Wang

Huang

et al. 2018

Acta Pharmacol Sin

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Silkworm cocoon was recorded to cure carbuncle in the Compendium of Materia Medica. Previous studies have demonstrated that the supplemental silk protein sericin exhibits anticancer activity. In the present study, we investigated the effects of silk fibroin peptide (SFP) extracted from silkworm cocoons against human lung cancer cells in vitro and in vivo and its possible anticancer mechanisms. SFP that we prepared had high content of glycine (~ 30%) and showed a molecular weight of ~ 10 kDa. Intragastric administration of SFP (30 g/kg/d) for 14 days did not affect the weights, vital signs, routine blood indices, and blood biochemical parameters in mice. MTT assay showed that SFP dose-dependently inhibited the growth of human lung cancer A549 and H460 cells in vitro with IC values of 9.921 and 9.083 mg/mL, respectively. SFP also dose-dependently suppressed the clonogenic activity of the two cell lines. In lung cancer H460 xenograft mice, intraperitoneal injection of SFP (200 or 500 mg/kg/d) for 40 days significantly suppressed the tumor growth, but did not induce significant changes in the body weight. We further examined the effects of SFP on cell cycle and apoptosis in H460 cells using flow cytometry, which revealed that SFP-induced cell cycle arrest at the S phase, and then promoted cell apoptosis. We demonstrated that SFP (20-50 mg/mL) dose-dependently downregulates Bcl-2 protein expression and upregulates Bax protein in H460 cells during cell apoptosis. The results suggest that SFP should be studied further as a novel therapeutic agent for the treatment of lung cancer.

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“…Specific phosphorylation on Ser552 or Ser675 on the C-terminus of β-catenin by PKA leads to an increase in nuclear translocation of β-catenin and subsequently enhanced TCF/ LEF transcriptional activity in many cell types 13 , 14 . Aberrant accumulation of β-catenin in nucleus caused by Wnt gene mutations in CRC is thus a potential target to search for specific chemotherapeutic agents 15 , 16 .…”

Section: Introductionmentioning

confidence: 99%

The anti-cancer activity of an andrographolide analogue functions through a GSK-3β-independent Wnt/β-catenin signaling pathway in colorectal cancer cells

Reabroi

Saeeng

Boonmuen

et al. 2018

Sci Rep

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The Wnt/β-catenin signaling pathway plays a key role in the progression of human colorectal cancers (CRCs) and is one of the leading targets of chemotherapy agents developed for CRC. The present study aimed to investigate the anti-cancer effects and molecular mechanisms of 19-O-triphenylmethyl andrographolide (RS-PP-050), an andrographolide analogue and determine its activity in the Wnt/β-catenin pathway. RS-PP-050 was found to potently inhibit the proliferation and survival of HT-29 CRC cells. It induces cell cycle arrest and promotes apoptotic cell death which was associated with the activation of PARP-1 and p53. Furthermore, RS-PP-050 exerts inhibitory effects on β-catenin transcription by suppressing T-cell factor/lymphocyte enhancer factor (TCF/LEF) activity in cells overexpressing β-catenin and by down-regulating the endogenous expression of Wnt target genes. RS-PP-050 also decreased the protein expression of the active form of β-catenin but functions independently of GSK-3β, a negative regulator of Wnt. Interestingly, RS-PP-050 extensively blocks phosphorylation at Ser675 of β-catenin which links to interference of the nuclear translocation of β-catenin and might contribute to Wnt inactivation. Collectively, our findings reveal the underlying anti-cancer mechanism of an andrographolide analogue and provide useful insight for exploiting a newly chemotherapeutic agent in Wnt/β-catenin-overexpressing CRC cells.

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BHX Inhibits the Wnt Signaling Pathway by Suppressing β-catenin Transcription in the Nucleus

Cited by 8 publications

References 36 publications

Cadherin 11 Inhibition Downregulates β-catenin, Deactivates the Canonical WNT Signalling Pathway and Suppresses the Cancer Stem Cell-Like Phenotype of Triple Negative Breast Cancer

Cadherin 11 Inhibition Downregulates β-catenin, Deactivates the Canonical WNT Signalling Pathway and Suppresses the Cancer Stem Cell-Like Phenotype of Triple Negative Breast Cancer

Silk fibroin peptide suppresses proliferation and induces apoptosis and cell cycle arrest in human lung cancer cells

The anti-cancer activity of an andrographolide analogue functions through a GSK-3β-independent Wnt/β-catenin signaling pathway in colorectal cancer cells

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