Upregulated N‐cadherin expression is associated with poor prognosis in epithelial‐derived solid tumours: A meta‐analysis

Luo, Yong; Yu, Ting; Zhang, Qiongwen; Fu, Qingyu; Hu, Yuzhu; Xiang, Mengmeng; Peng, Hao; Zheng, Ting; Lu, Li; Shi, Huashan

doi:10.1111/eci.12903

Cited by 41 publications

(30 citation statements)

References 73 publications

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“…In various malignancies including breast cancer, cells acquire motility and invasiveness by upregulating N-cadherin during EMT [27][28][29]. We also reported that N-cadherin is associated with tumor aggressiveness in esophageal carcinoma [30], and others demonstrated the value of N-cadherin as a marker of invasive, malignant tumors [29,31], supporting our finding that N-cadherin expression in PB may be a predictive biomarker of NM. The expression level of N-cadherin may represent the real-time metastatic potential of tumor cells ( Figure 3e).…”

Section: Discussionsupporting

confidence: 86%

N-Cadherin mRNA Levels in Peripheral Blood Could Be a Potential Indicator of New Metastases in Breast Cancer: A Pilot Study

Masuda

Ueo²,

Kai

et al. 2020

IJMS

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Background: There is growing evidence that patients with metastatic breast cancer whose disease progresses from a new metastasis (NM) have a worse prognosis than that of patients whose disease progresses from a pre-existing metastasis. The aim of this pilot study is to identify a blood biomarker predicting NM in breast cancer. Methods: The expression of epithelial (cytokeratin 18/19) or mesenchymal (plastin-3, vimentin, and N-cadherin) markers in the peripheral blood (PB) of recurrent breast cancer patients undergoing chemotherapy with eribulin or S-1 was measured over the course of treatment by RT-qPCR. The clinical significance of preoperative N-cadherin expression in the PB or tumor tissues of breast cancer patients undergoing curative surgery was assessed by RT-qPCR or using public datasets. Finally, N-cadherin expression in specific PB cell types was assessed by RT-qPCR. Results: The expression levels of the mesenchymal markers N-cadherin and vimentin were high in the NM cases, whereas that of the epithelial marker cytokeratin 18 was high in the pre-existing metastasis cases. High preoperative N-cadherin expression in PB or tumor tissues was significantly associated with poor recurrence-free survival. N-cadherin was expressed mainly in polymorphonuclear leukocytes in PB. Conclusion: N-cadherin mRNA levels in blood may serve as a novel prognostic biomarker predicting NM, including recurrence, in breast cancer patients.

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Section: Discussionsupporting

confidence: 86%

N-Cadherin mRNA Levels in Peripheral Blood Could Be a Potential Indicator of New Metastases in Breast Cancer: A Pilot Study

Masuda

Ueo²,

Kai

et al. 2020

IJMS

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“…Aberrant N-cadherin expression has a clear role in tumour progression in epithelial cancer cells and has been associated with poor overall patient survival in diverse types of cancers [38]. Accordingly, we have found that the presence of leader mesenchymal cells, either N+ cancer cells or CAFs, is significantly associated with distant metastasis and low overall survival in patients with head and neck SCC.…”

Section: Discussionmentioning

confidence: 66%

The Leader Position of Mesenchymal Cells Expressing N-Cadherin in the Collective Migration of Epithelial Cancer

Sáenz‐de‐Santa‐María

Celada

Chiara

2020

Cells

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Understanding how heterogeneous cancer cell populations migrate collectively is of paramount importance to arrest metastasis. Here, we applied 3D culture-based approaches for in vitro modeling of the collective migration of squamous carcinoma cells and examine the impact of epithelial and mesenchymal cell interactions on this type of migration. We show that both mesenchymal N-cadherin-expressing cancer cells and cancer-associated fibroblasts cooperate in collective migration of epithelial cancer cells by leading their collective migration. This was consistent with the observed distribution of E-cadherin/N-cadherin in the human carcinoma tissues of head and neck. The presence of "leader" mesenchymal cancer cells or "leader" fibroblasts was significantly associated with metastasis development, recurrent disease and low overall disease survival in head and neck squamous cell carcinomas (HNSCC). In silico analysis of independent public datasets revealed that increased N-cadherin expression in the heterogeneous cancer tissues is associated with disease progression not only in HNSCC but also in other prevalent tumors, such as colorectal, breast and lung cancer. Collectively, our data highlight the importance of mesenchymal cells in collective cell migration and disease progression, findings that may have a broad significance in cancer, especially in those in which aberrant N-cadherin expression negatively impacts disease survival.

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“…We also observed that D14 and D15 downregulate vimentin , N-cadherin , Slug , and β-catenin gene expression, especially in p53-expressing osteosarcoma cells. A high expression of these genes is associated with cancer metastasis and poor prognosis [ 40 , 41 , 42 , 43 ]. On the other hand, the inhibition of vimentin , N-cadherin , Slug , and β-catenin can reduce invasion, migration, and metastases development [ 44 , 45 , 46 , 47 ].…”

Section: Discussionmentioning

confidence: 99%

Chalcone Derivatives 4′-Amino-1-Naphthyl-Chalcone (D14) and 4′-Amino-4-Methyl-1-Naphthyl-Chalcone (D15) Suppress Migration and Invasion of Osteosarcoma Cells Mediated by p53 Regulating EMT-Related Genes

Seba

Silva

Santos

et al. 2018

IJMS

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Osteosarcoma (OS) is a primary malignant bone tumor that mainly affects children, adolescents, and young adults. The inhibition of metastasis is a main strategy of OS therapy since the development of metastatic disease due to drug resistance remains the most important cause of death from this cancer. Considering the severe side effects of current OS chemotherapy, the identification of anti-metastatic drugs with reduced toxicity is of great interest. Chalcones are polyphenols with a basic structure consisting of an α-, β-unsaturated carbonyl system linking two aryl rings. These compounds exhibit anticancer activity against a variety of tumor cell lines through multiple mechanisms, including the regulation of the tumor-suppressor protein p53 and its target genes. An important process regulated by p53 is epithelial-mesenchymal transition (EMT), which facilitates tumor metastasis by conferring migratory and invasive properties to cancer cells. The activation of p53 can revert EMT and reduce migration and invasion. This study aimed to examine the inhibitory effects of two 4′-aminochalcones on the migration/invasion of the U2OS (p53+/+) and SAOS-2 (p53−/−) OS cell lines as well as the underlying molecular mechanisms. Cell viability was examined by MTT assay. Transwell assays were used to evaluate the migratory and invasive ability of the cells. The two 4′-aminochalcones showed low capacity to inhibit the viability of OS cells independent of p53 status, but preferentially suppressed the migration of U2OS cells and of a SAOS-2 cell line expressing p53. Invasion was strongly inhibited by both chalcones independent of p53 status. RT-PCR, zymography, and Western blot were used to study the expression of matrix metalloproteinases and EMT markers after treatment with the chalcones. The results indicated that the 4′-aminochalcone-induced antimigratory and anti-invasive effects are potentially associated with the inhibition of extracellular matrix (ECM) enzymatic degradation in OS cells and with the modulation of EMT genes. These effects probably result from the induced increase of p53 protein expression by the two chalcones. In conclusion, chalcones D14 and D15 have potential anti-metastatic activity mediated by p53 that can be exploited for OS treatment.

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Upregulated N‐cadherin expression is associated with poor prognosis in epithelial‐derived solid tumours: A meta‐analysis

Cited by 41 publications

References 73 publications

N-Cadherin mRNA Levels in Peripheral Blood Could Be a Potential Indicator of New Metastases in Breast Cancer: A Pilot Study

N-Cadherin mRNA Levels in Peripheral Blood Could Be a Potential Indicator of New Metastases in Breast Cancer: A Pilot Study

The Leader Position of Mesenchymal Cells Expressing N-Cadherin in the Collective Migration of Epithelial Cancer

Chalcone Derivatives 4′-Amino-1-Naphthyl-Chalcone (D14) and 4′-Amino-4-Methyl-1-Naphthyl-Chalcone (D15) Suppress Migration and Invasion of Osteosarcoma Cells Mediated by p53 Regulating EMT-Related Genes

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