Wnt/β-Catenin Pathway-Regulated Fibromodulin Expression Is Crucial for Breast Cancer Metastasis and Inhibited by Aspirin

Khan, Fahim Ullah; Owusu-Tieku, Nana Yaa Gyaama; Dai, Xiaoyong; Liu, Kewei; Wu, Yanping; Tsai, Hsiang‐i; Chen, Hongbo; Sun, Chunhui; Huang, Laiqiang

doi:10.3389/fphar.2019.01308

Cited by 24 publications

(18 citation statements)

References 52 publications

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“…Wnt signaling proteins interact with the frizzled family of cell-surface receptors and activate the proteins of the disheveled family, which in turn results in the inhibition of proteolytic degradation of β-catenin. Subsequently, stabilized β-catenin is translocated into the nucleus, leading to the transcription of target genes such as C-Myc and Cyclin D1, which are involved in determining cell migration, cytoskeletal activity, cell polarity, and cellular differentiation ( 39 , 40 ). Recently, the overexpression of Wnt pathway has been observed in breast, lung, and hematopoietic malignancies and contributes to tumor recurrence ( 41 ).…”

Section: Chemoresistance Mechanisms In Brcamentioning

confidence: 99%

Chemoresistance and Metastasis in Breast Cancer Molecular Mechanisms and Novel Clinical Strategies

et al. 2021

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Breast cancer is the most common malignant tumor in females worldwide. Chemotherapy is the standard breast cancer treatment; however, chemoresistance is often seen in patients with metastatic breast cancer. Owing to high heterogeneity, the mechanisms of breast cancer chemoresistance and metastasis have not been fully investigated. The possible molecular mechanisms of chemoresistance in breast cancer include efflux transporters, signaling pathways, non-coding RNAs, and cancer stem cells. However, to overcome this hurdle, the use of novel clinical strategies such as drug carriers, immunotherapy, and autophagy regulation, are being investigated. The goal of this review is to summarize the current data about the molecular mechanisms of breast cancer chemoresistance and the novel clinical strategies; thus, providing a useful clinical tool to explore optimal treatment for breast cancer.

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Section: Chemoresistance Mechanisms In Brcamentioning

confidence: 99%

Chemoresistance and Metastasis in Breast Cancer Molecular Mechanisms and Novel Clinical Strategies

et al. 2021

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“…Khan et al . showed that in human breast cancer patients, the Wnt/β-catenin signaling is highly activated, suggesting poor prognosis in patients with activated Wnt/β-catenin signaling ( 12 ). A study has also shown that the Wnt/β-catenin signaling is also highly active in CMGTs ( 33 ).…”

Section: Discussionmentioning

confidence: 99%

“…In addition, Aspirin in a combination with the cisplatin inhibit the migration of non-small cell lung carcinoma stem-like cells by targeting mTOR-Akt axis ( 11 ). And Khan FU using cell lines, animal model and database analysis shows that Aspirin inhibits breast cancer cell migration and invasion by attenuating Wnt/β-catenin signaling and suppressing fibromodulin expression ( 12 ). On the other hand, in osteosarcoma cell lines Aspirin reduced cell viability in a dose- and time-dependent manner ( 13 ).…”

Section: Introductionmentioning

confidence: 99%

“…In malignant tumor cells, including colon cancer, breast cancer, liver cancer, and lung cancer, β-catenin accumulates within cytoplasm and nucleus, leading to abnormal activation of its downstream target genes, such as c-myc, cyclin D1, and PPAR-δ ( 18 ). Many researchers determined that the anti-tumor effect of Aspirin is related to Wnt/β-catenin signaling ( 12 , 19 - 22 ). However, these studies have mainly focused on aspirin inhibiting tumor proliferation and promoting apoptosis, and less on tumor metastasis and its exact molecular mechanism has not yet been clarified.…”

Section: Introductionmentioning

confidence: 99%

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Aspirin inhibits proliferation and metastasis of canine mammary gland tumor cells through Wnt signaling axis

Xu¹,

Hu²,

Liu³

2021

Transl Cancer Res TCR

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Background Breast cancer is one of the most common, lethal types of neoplasia. The high mortality is largely due to rapid growth and distal metastasis. Epithelial-mesenchymal transition (EMT) and increased activity of matrix metalloproteinases (MMPs), which are related to tumor aggressiveness and progression, are known to be essential processes. Aspirin, a classic anti-inflammatory treatment, has been shown to inhibit the different types of cancer, though its research have yet to be elucidated and remain controversial. Methods We set out to elucidate the mechanism of Aspirin against the metastasis of canine mammary gland tumor cells (CMGTs), and provide theoretical support for the rational use of non-steroidal anti-inflammatory drugs. Firstly, we utilized CCK8, wound healing and transwell invasion assays to determine the effect of Aspirin on proliferation and migration of CMGTs. Next, we determined the effect of Aspirin on Wnt/β-catenin signaling by cellular immunofluorescence and western blot analysis. Finally, Wnt/β-catenin pathway activating agent (Wnt3a) and inhibitor (FH535) were utilized to further validate the relationship between Aspirin and Wnt/β-catenin signaling. Results The results indicated that Aspirin inhibits proliferation and migration of CMGTs in a time-and concentration-dependent manner. Moreover, the inhibitory effect of Aspirin on CMGTs was reduced upon addition of a Wnt pathway activating agent (Wnt3a), while the effect following the addition of Wnt pathway inhibitor (FH535) remained the same as that of Aspirin. Conclusions Our study demonstrates that Aspirin can inhibit the proliferation, migration and invasion by inhibiting Wnt/β-catenin signaling, which suggest it can be a promising tool for deterring metastasis of CMGTs.

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“…Both of Dickkopf-related protein (DKK)-1 (inhibitor of Wnt) and ICG-001 (inhibitor of β-catenin) could attenuate peritoneal angiogenesis and reduce VEGF [ 11 ]. Interestingly, HDAC6 was reported to regulate β-catenin by deacetylation, leading to β-catenin phosphorylation and activation of downstream signal molecules [ 46 ]. Further research indicated that HDAC6-induced β-catenin deacetylation (K345) is essential for Wnt signal transduction [ 47 ].…”

Section: Discussionmentioning

confidence: 99%

Elevated expression of HDAC6 in clinical peritoneal dialysis patients and its pathogenic role on peritoneal angiogenesis

Shi

Tao

et al. 2020

Renal Failure

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Peritoneal dialysis (PD) is an important renal replacement therapy for end-stage renal disease (ESRD) patients. However, its complications, such as peritoneal fibrosis (PF) and angiogenesis can cause ultrafiltration failure and PD termination. Histone deacetylase 6 (HDAC6) has been demonstrated to be involved in PF. However, its underlying role in peritoneal angiogenesis is still unknown and clinical value needs to be explored. In this study, we analyzed the expression of HDAC6 in the peritoneum from patients with non-PD and PD-related peritonitis and dialysis effluent from stable PD patients. Our study revealed that HDAC6 expressed highly in the peritoneum with peritonitis and co-stained with α-smooth muscle actin (α-SMA), a biomarker of the myofibroblast. And the level of HDAC6 in the dialysate increased with time and positively correlated with transforming growth factor-β1 (TGF-β1), interleukin-6 (IL-6) and vascular endothelial growth factor (VEGF), and negatively with cancer antigen 125 (CA125). In vitro , blockading HDAC6 with a selective inhibitor tubastatin A (TA) or silencing HDAC6 with a small interfering RNA (siRNA) prominently decreased IL-6-stimulated VEGF expression in cultured human peritoneal mesothelial cells (HPMCs), and inhibited proliferation and vasoformation of human umbilical vein endothelial cells (HUVECs). TA or HDAC6 siRNA also suppressed the expression of Wnt1, β-catenin, and the phosphorylation of STAT3 in IL-6-treated HPMCs. In summary, HDAC6 inhibition protects against PD-induced angiogenesis through suppression of IL-6/STAT3 and Wnt1/β-catenin signaling pathway, subsequently reducing the VEGF production and angiogenesis. It could become a new therapeutic target or forecast biomarker for PF, inflammation, and angiogenesis in the future.

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Wnt/β-Catenin Pathway-Regulated Fibromodulin Expression Is Crucial for Breast Cancer Metastasis and Inhibited by Aspirin

Cited by 24 publications

References 52 publications

Chemoresistance and Metastasis in Breast Cancer Molecular Mechanisms and Novel Clinical Strategies

Chemoresistance and Metastasis in Breast Cancer Molecular Mechanisms and Novel Clinical Strategies

Aspirin inhibits proliferation and metastasis of canine mammary gland tumor cells through Wnt signaling axis

Elevated expression of HDAC6 in clinical peritoneal dialysis patients and its pathogenic role on peritoneal angiogenesis

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