scholarly journals AT2 Receptor Mediated Activation of the Tyrosine Phosphatase PTP1B Blocks Caveolin-1 Enhanced Migration, Invasion and Metastasis of Cancer Cells

Cancers ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 1299 ◽  
Author(s):  
Martínez-Meza ◽  
Díaz ◽  
Sandoval-Bórquez ◽  
Valenzuela-Valderrama ◽  
Díaz-Valdivia ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Metastatic Cancer ◽  
Tyrosine Phosphatase ◽  
Transendothelial Migration ◽  
Receptor Protein ◽  
Invasion And Metastasis ◽  
Cancer Disease ◽  
Caveolin 1

: The renin–angiotensin receptor AT2R controls systemic blood pressure and is also suggested to modulate metastasis of cancer cells. However, in the latter case, the mechanisms involved downstream of AT2R remain to be defined. We recently described a novel Caveolin-1(CAV1)/Ras-related protein 5A (Rab5)/Ras-related C3 botulinum toxin substrate 1 (Rac1) signaling axis that promotes metastasis in melanoma, colon, and breast cancer cells. Here, we evaluated whether the antimetastatic effect of AT2R is connected to inhibition of this pathway. We found that murine melanoma B16F10 cells expressed AT2R, while MDAMB-231 human breast cancer cells did not. AT2R activation blocked migration, transendothelial migration, and metastasis of B16F10(cav-1) cells, and this effect was lost when AT2R was silenced. Additionally, AT2R activation reduced transendothelial migration of A375 human melanoma cells expressing CAV1. The relevance of AT2R was further underscored by showing that overexpression of the AT2R in MDA-MB-231 cells decreased migration. Moreover, AT2R activation increased non-receptor protein tyrosine phosphatase 1B (PTP1B) activity, decreased phosphorylation of CAV1 on tyrosine-14 as well as Rab5/Rac1 activity, and reduced lung metastasis of B16F10(cav-1) cells in C57BL/6 mice. Thus, AT2R activation reduces migration, invasion, and metastasis of cancer cells by PTP1B-mediated CAV1 dephosphorylation and inhibition of the CAV1/Rab5/Rac-1 pathway. In doing so, these observations open up interesting, novel therapeutic opportunities to treat metastatic cancer disease.

scholarly journals Down-Regulation of WAVE3, a Metastasis Promoter Gene, Inhibits Invasion and Metastasis of Breast Cancer Cells

2007 ◽  
Vol 170 (6) ◽  
pp. 2112-2121 ◽  
Author(s):  
Khalid Sossey-Alaoui ◽  
Alfiya Safina ◽  
Xiurong Li ◽  
Mary M. Vaughan ◽  
David G. Hicks ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Invasion And Metastasis ◽  
Down Regulation ◽  
Promoter Gene

scholarly journals Metformin-induced caveolin-1 expression promotes T-DM1 drug efficacy in breast cancer cells

2018 ◽  
Vol 8 (1) ◽  
Author(s):  
Yuan-Chiang Chung ◽  
Ching-Ming Chang ◽  
Wan-Chen Wei ◽  
Ting-Wei Chang ◽  
King-Jen Chang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Drug Efficacy ◽  
Caveolin 1

Caveolin-1 overexpression is associated with docetaxel resistance in breast cancer cells

2007 ◽  
Vol 33 (9) ◽  
pp. 1095-1095
Author(s):  
J SANGRITHIWALLACE ◽  
I BROWN ◽  
S HEYS ◽  
A SCHOFIELD
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Caveolin 1 ◽  
Docetaxel Resistance

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

Cancers ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 1946 ◽  
Author(s):  
Junyu Cen ◽  
Lingyun Feng ◽  
Huichuan Ke ◽  
Lifeng Bao ◽  
Lin Z. Li ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Endothelial Cells ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Breast Cancer Cells ◽  
Transendothelial Migration ◽  
Intercellular Junction ◽  
Malignant Cells ◽  
Junction Proteins

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.

scholarly journals Protein Disulphide Isomerase A1 Is Involved in the Regulation of Breast Cancer Cell Adhesion and Transmigration via Lung Microvascular Endothelial Cells

Cancers ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 2850
Author(s):  
Marta Stojak ◽  
Magdalena Milczarek ◽  
Anna Kurpinska ◽  
Joanna Suraj-Prazmowska ◽  
Patrycja Kaczara ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Endothelial Cells ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Breast Cancer Cells ◽  
Transendothelial Migration ◽  
Microvascular Endothelial Cells ◽  
Protein Disulphide Isomerase ◽  
Cellular Bioenergetics ◽  
Microvascular Endothelial

Cancer cell cross-talk with the host endothelium plays a crucial role in metastasis, but the underlying mechanisms are still not fully understood. We studied the involvement of protein disulphide isomerase A1 (PDIA1) in human breast cancer cell (MCF-7 and MDA-MB-231) adhesion and transendothelial migration. For comparison, the role of PDIA1 in proliferation, migration, cell cycle and apoptosis was also assessed. Pharmacological inhibitor, bepristat 2a and PDIA1 silencing were used to inhibit PDIA1. Inhibition of PDIA1 by bepristat 2a markedly decreased the adhesion of breast cancer cells to collagen type I, fibronectin and human lung microvascular endothelial cells. Transendothelial migration of breast cancer cells across the endothelial monolayer was also inhibited by bepristat 2a, an effect not associated with changes in ICAM-1 expression or changes in cellular bioenergetics. The silencing of PDIA1 produced less pronounced anti-adhesive effects. However, inhibiting extracellular free thiols by non-penetrating blocker p-chloromercuribenzene sulphonate substantially inhibited adhesion. Using a proteomic approach, we identified that β1 and α2 integrins were the most abundant among all integrins in breast cancer cells as well as in lung microvascular endothelial cells, suggesting that integrins could represent a target for PDIA1. In conclusion, extracellular PDIA1 plays a major role in regulating the adhesion of cancer cells and their transendothelial migration, in addition to regulating cell cycle and caspase 3/7 activation by intracellular PDIA1. PDIA1-dependent regulation of cancer–endothelial cell interactions involves disulphide exchange and most likely integrin activation but is not mediated by the regulation of ICAM-1 expression or changes in cellular bioenergetics in breast cancer or endothelial cells.

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