Niclosamide sensitizes triple-negative breast cancer cells to ionizing radiation in association with the inhibition of Wnt/β-catenin signaling

Yin, Lina; Gao, Yun; Zhang, Xuxia; Wang, Jing; Ding, Defang; Zhang, Yaping; Zhang, Junxiang; Chen, Honghong

doi:10.18632/oncotarget.9704

Cited by 43 publications

(37 citation statements)

References 48 publications

(55 reference statements)

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“…As previously reported, the aberrant expression of Wnt3a was also found in several human malignancies, including glioblastoma [16,17], mammary adenocarcinoma [18,19], colon carcinoma [20], lung cancer [21], prostate cancer [22], malignant mesothelioma [23], esophageal squamous cell carcinoma [24], hepatocellular carcinoma [25][26][27], and melanoma [28]. In these malignant tumors, Wnt3a expression is closely related to tumor growth, metastasis, chemo-/ radio-resistance and maintenance of CSC characteristics.…”

Section: Discussionsupporting

confidence: 63%

Wnt3a protein overexpression predicts worse overall survival in laryngeal squamous cell carcinoma

Zhang

Chen

et al. 2019

J. Cancer

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As a classical ligand in the canonical Wnt/β-catenin signaling pathway, the role of Wnt3a in laryngeal squamous cell carcinoma (LSCC) remains unclear. Therefore, the expression pattern of the Wnt3a protein in 222 primary LSCC, and 19 corresponding adjacent non-carcinoma specimens, was detected by immunohistochemistry and further correlated with clinicopathological parameters. The results showed that LSCC tissue expressed higher levels of the Wnt3a protein when compared to the corresponding adjacent non-cancerous tissues. High expression of Wnt3a was closely related to histological grade (P = 0.031), clinical stage (I+II / III+IV; P = 0.004), and lymph node metastasis (P = 0.03). Kaplan-Meier analysis evidenced that a worse overall survival (OS) was correlated to the group with high Wnt3a expression (P = 0.003). When stratified survival analyses were performed, patients with lymph node metastasis/advanced clinical stages and high Wnt3a expression had worse OS rates than patients with other features (P < 0.001). Finally, multivariate analysis showed that Wnt3a expression was an independent prognosis factor for LSCC patients. The current findings suggest that Wnt3a is tightly related to the LSCC progression and could serve as a valuable clinic biomarker for LSCC patients.

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Section: Discussionsupporting

confidence: 63%

Wnt3a protein overexpression predicts worse overall survival in laryngeal squamous cell carcinoma

Zhang

Chen

et al. 2019

J. Cancer

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“…Niclosamide is an anti-helminthic drug introduced in the 1950's, and has been used to treat parasitic infections in millions of patients worldwide [8]. It has been shown to effect a number of host cellular signaling pathways, including Wnt [9], Notch [10], mTOR, NF-κB [11], and STAT3 [12]. This broad activity has led to its evaluation as a therapeutic agent for a number of cancers, including breast, colon, ovarian, prostate, and others [13][14][15][16].…”

Section: Introductionmentioning

confidence: 99%

Dual activity of niclosamide to suppress replication of integrated HIV-1 and Mycobacterium tuberculosis (Beijing)

Fan

Files

et al. 2019

Tuberculosis

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The human immunodeficiency virus (HIV) pandemic is driving the re-emergence of tuberculosis (TB) as a global health threat, both by increasing the susceptibility of HIV-infected people to infection with Mycobacterium tuberculosis (Mtb), and increasing the rate of emergence of drug-resistant Mtb. There are several other clinical challenges for treatment of co-infected patients including: expense, pill burden, toxicity, and malabsorption that further necessitate the search for new drugs that may be effective against both pathogens simultaneously. The anti-helminthic niclosamide has been shown to have activity against a laboratory strain of Mtb in liquid culture while bacteriostatic activity against non-replicating M. abscessus was also recently described. Here we extend these findings to further demonstrate that niclosamide inhibits mycobacterial growth in infected human macrophages and mediates potent bacteriostatic activity against the virulent Mtb Beijing strain. Importantly, we provide the first evidence that niclosamide inhibits HIV replication in human macrophages and Jurkat T cells through post-integration effects on pro-virus transcription. The dual antiviral and anti-mycobacterial activity was further observed in an in vitro model of HIV and Mtb co-infection using human primary monocyte-derived macrophages. These results support further investigation of niclosamide and derivatives as anti-retroviral/antimycobacterial agents that may reduce clinical challenges associated with multi-drug regimens and drug resistance.

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“…Targeting focal adhesion kinase could provide a potential therapeutic approach for improving radiotherapy sensitivity (42). A recent study has identified that the Wnt/β-catenin signaling pathway serves an important role in the development of radioresistance and the inhibition of Wnt/β-catenin signaling may have significant radiosensitizing effects (26). The current study has revealed pathways that may contribute to the CRT response of rectal cancer and may be potential predictive biomarkers.…”

Section: Discussionmentioning

confidence: 72%

“…With regard to the KEGG pathway enrichment results, the upregulated DE genes in CRT responders were mainly involved in pathways including base excision repair and homologous recombination, while downregulated DE genes in CRT responders were enriched in pathways including the Ras signaling pathway, FoxO signaling pathway, focal adhesion and Wnt signaling pathway. These pathways were also indicated to be highly associated with radiation response (23)(24)(25)(26). The seven hub nodes (TOP2B, MAPK8, DLG4, GCG, NGF, INSR and ARRB2) were associated with the Ras signaling pathway, MAPK signaling pathway and FoxO signaling pathway.…”

Section: Identification Of Crt Response-associated Functions and Pathmentioning

confidence: 92%

Identification of potential genes and pathways for response prediction of neoadjuvant chemoradiotherapy in patients with rectal cancer by systemic biological analysis

et al. 2018

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Currently, neoadjuvant chemoradiotherapy (CRT) followed by radical surgery is the standard of care for locally advanced rectal cancer. However, to the best of our knowledge, there are no effective biomarkers for predicting patients who may benefit from neoadjuvant treatment. The aim of the current study was to screen potential crucial genes and pathways associated with the response to CRT in rectal cancer, and provide valid biological information to assist further investigation of CRT optimization. In the current study, differentially expressed (DE) genes were identified from the tumor samples of responders and non-responders to neoadjuvant CRT in the GSE35452 gene expression profile. Seven hub genes and one significant module were identified from the protein-protein interaction (PPI) network. Functional enrichment analysis of all the DE genes and the hub genes, retrieved from PPI network analysis, revealed their associations with CRT response. Genes were identified that may be used to discriminate patients who would or would not clinically benefit from neoadjuvant CRT. Several important pathways enriched by the DE genes, hub genes and selected module were identified, and revealed to be closely associated with radiation response, including excision repair, homologous recombination, Ras signaling pathway, the forkhead box O signaling pathway, focal adhesion and the Wnt signaling pathway. In conclusion, the current study demonstrated that the identified gene signatures and pathways may be used as molecular biomarkers for predicting CRT response. Furthermore, combinations of these biomarkers may be helpful for optimizing CRT treatment and promoting understanding of the molecular basis of response differences; this needs to be confirmed by further experiments.

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Niclosamide sensitizes triple-negative breast cancer cells to ionizing radiation in association with the inhibition of Wnt/β-catenin signaling

Cited by 43 publications

References 48 publications

Wnt3a protein overexpression predicts worse overall survival in laryngeal squamous cell carcinoma

Wnt3a protein overexpression predicts worse overall survival in laryngeal squamous cell carcinoma

Dual activity of niclosamide to suppress replication of integrated HIV-1 and Mycobacterium tuberculosis (Beijing)

Identification of potential genes and pathways for response prediction of neoadjuvant chemoradiotherapy in patients with rectal cancer by systemic biological analysis

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