S100P and Ezrin promote trans-endothelial migration of triple negative breast cancer cells

Kikuchi, Keiko; McNamara, Keely May; Miki, Yasuhiro; Iwabuchi, Erina; Kanai, Ayako; Miyashita, Minoru; Ishida, Toru; Sasano, Hironobu

doi:10.1007/s13402-018-0408-2

Cited by 32 publications

(28 citation statements)

References 46 publications

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“…Ezrin is mainly expressed at the top of cell surface and participates in maintaining the polarity of epithelial cells . Recent studies have found that ezrin participates in cells and bases interaction by regulating adhesion molecules and signal transduction pathways which may play an important role in the invasion and metastasis of cancer cells …”

Section: Discussionmentioning

confidence: 99%

High expression of EZR (ezrin) gene is correlated with the poor overall survival of breast cancer patients

Zhang

Zhang²,

Rongge

et al. 2019

Thoracic Cancer

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Background To evaluate the EZR (ezrin) gene expression in breast cancer and correlation with the prognosis through bioinformatics analysis and immunohistochemistry assay. Methods EZR gene expression in breast cancer and corresponding normal breast tissue was compared in the TCGA database. Protein‐protein interaction (PPI) network relevant EZR was established through the STRING database. The correlation between EZR expression and prognosis of breast cancer was analyzed by the log‐rank analysis from the TCGA. Ezrin protein (coded by EZR) expression was also examined by immunohistochemistry assay in 120 breast cancer patients. Results EZR expression level in tumor tissue was significantly upregulated compared to that of normal breast tissue of breast cancer patients (P < 0.05). In the PPI analysis, there were 51 nodes and 455 edges in the network. The top 10 hub genes of the network were identified. High expression of EZR mRNA was correlated with poor overall survival (OS) of the breast cancer patients (HR = 1.40, P = 0.038). However, the disease‐free survival (DFS) of breast cancer patients did not correlate with the EZR mRNA level (HR = 0.86, P = 0.44). The ezrin protein expression was positive with uniform brown‐yellow granules in the cell membrane, cavity surface and cytoplasm of the breast cancer cells. Of the included 120 cancer samples, 98 cases were positive for ezrin expression and 22 were negative. No correlation was found between ezrin expression site and patients’ clinicopathological features. Conclusion EZR is upregulated in breast cancer and can be used as potential biomarker for overall survival.

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Section: Discussionmentioning

confidence: 99%

High expression of EZR (ezrin) gene is correlated with the poor overall survival of breast cancer patients

Zhang

Zhang²,

Rongge

et al. 2019

Thoracic Cancer

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“…S100P expression is elevated in TNBC tissues (21) and associated with poor survival of the TNBC patients (22). TNBC patients with the low cytoplasmic levels of both S100P and Ezrin have been shown to confer a better disease-free survival (DFS) compared to other TNBC patients (23). S100P is thought to exerts its oncogenic activities via the activation of receptor for advanced glycation end products (RAGE) (24).…”

Section: Introductionmentioning

confidence: 99%

“…Additionally, S100P dimers, formed in response to the increase in cellular calcium concentrations, can bind and activate the cytoplasmic protein Ezrin ( 7 ). This interaction promotes trans-endothelial migration (TEM) in patients with lung cancer, pancreatic cancer, and TNBC ( 23 ). Moreover, S100P enhances cell proliferation by upregulating cyclin D1 and CDK2 in human hepatocellular carcinoma ( 26 ).…”

Section: Introductionmentioning

confidence: 99%

Calcium-Binding Protein S100P Promotes Tumor Progression but Enhances Chemosensitivity in Breast Cancer

et al. 2020

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Background: Chemoresistance remains one of the obstacles to overcome in the treatment of breast cancer. S100 calcium-binding protein P (S100P) has been observed to be overexpressed in several cancers and has been associated with drug resistance, metastasis, and prognosis. However, the role of S100P in chemoresistance in breast cancer has not been thoroughly determined. Methods: Immunohistochemistry was used to evaluate the expression level of S100P protein in 22 pairs (pre-chemo and post-chemo) of breast cancer tissue from patients who underwent neoadjuvant chemotherapy. The influence of S100P on the biological behavior and chemosensitivity of breast cancer cells was then investigated. Results: The protein level of S100P in breast cancer tissue was significantly higher than in benign fibroadenoma (p < 0.001). The S100P expression level was shown to be decreased by 46.55% after neoadjuvant chemotherapy (p = 0.015). Subgroup analysis revealed that S100P reduction (57.58%) was mainly observed in the HER2+ tumors (p = 0.027). Our in vitro experiments showed that the knockdown of S100P suppressed the proliferation, adhesion, migrative and invasive abilities of T47D and SK-BR-3 breast cancer cells. We further demonstrated that this knockdown increased the chemoresistance to paclitaxel and cisplatin in SK-BR-3 cells. We found S100P exerted its function by upregulating NF-κB, CCND1 and Vimentin, but downregulating E-cadherin. Conclusion: S100P promotes the aggressive properties of breast cancer cells and may be considered as a promising therapeutic target. Moreover, S100P can be used to predict the therapeutic effect of chemotherapy in HER2+ breast cancer patients.

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“…For example, the cytokine-transforming growth factor-β (TGF-β) signaling can enhance intravasation, at least in part, through induction of epithelial-mesenchymal transition (EMT) [3]. Single and double small interfering RNA (siRNA)-mediated knockdown of S100 calcium-binding protein P (S100P) and Ezrin in the triple-negative breast cancer-derived cells significantly inhibited their transendothelial migration of malignant and destabilized the intercellular junctions of endothelial cells [4]. These processes are closely related to tumor microenvironments.…”

Section: Introductionmentioning

confidence: 99%

Exosomal Thrombospondin-1 Disrupts the Integrity of Endothelial Intercellular Junctions to Facilitate Breast Cancer Cell Metastasis

Cen

Feng

et al. 2019

Cancers

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Transendothelial migration of malignant cells plays an essential role in tumor progression and metastasis. The present study revealed that treating human umbilical vein endothelial cells (HUVECs) with exosomes derived from metastatic breast cancer cells increased the number of cancer cells migrating through the endothelial cell layer and impaired the tube formation of HUVECs. Furthermore, the expression of intercellular junction proteins, including vascular endothelial cadherin (VE-cadherin) and zona occluden-1 (ZO-1), was reduced significantly in HUVECs treated with carcinoma-derived exosomes. Proteomic analyses revealed that thrombospondin-1 (TSP1) was highly expressed in breast cancer cell MDA-MB-231-derived exosomes. Treating HUVECs with TSP1-enriched exosomes similarly promoted the transendothelial migration of malignant cells and decreased the expression of intercellular junction proteins. TSP1-down regulation abolished the effects of exosomes on HUVECs. The migration of breast cancer cells was markedly increased in a zebrafish in vivo model injected with TSP1-overexpressing breast cancer cells. Taken together, these results suggest that carcinoma-derived exosomal TSP1 facilitated the transendothelial migration of breast cancer cells via disrupting the intercellular integrity of endothelial cells.

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S100P and Ezrin promote trans-endothelial migration of triple negative breast cancer cells

Cited by 32 publications

References 46 publications

High expression of EZR (ezrin) gene is correlated with the poor overall survival of breast cancer patients

High expression of EZR (ezrin) gene is correlated with the poor overall survival of breast cancer patients

Calcium-Binding Protein S100P Promotes Tumor Progression but Enhances Chemosensitivity in Breast Cancer

Exosomal Thrombospondin-1 Disrupts the Integrity of Endothelial Intercellular Junctions to Facilitate Breast Cancer Cell Metastasis

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