scholarly journals Potassium channel-driven bioelectric signaling regulates metastasis in triple-negative breast cancer

2021 ◽  
Author(s):  
Samantha L Payne ◽  
Priyanka Ram ◽  
Deepti H Srinivasan ◽  
Thanh T Le ◽  
Michael Levin ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Potassium Channel ◽  
Cancer Cell ◽  
Metastatic Disease ◽  
Triple Negative Breast Cancer ◽  
Cell Invasion ◽  
Triple Negative ◽  
Cancer Cell Invasion ◽  
Invasion And Metastasis

There is a critical need to better understand the mechanisms that drive local cell invasion and metastasis to develop new therapeutics targeting metastatic disease. Bioelectricity is an important mediator of cellular processes and changes in the resting membrane potential (RMP) are associated with increased cancer cell invasion. However, the mechanism is not well understood. Our data demonstrate that altering the RMP of triple-negative breast cancer (TNBC) cells by manipulating potassium channel expression increases in vitro invasion, in vivo tumor growth, and metastasis, and is accompanied by changes in gene expression associated with cell adhesion. We describe a novel mechanism for RMP-mediated cell migration involving cadherin-11 and the MAPK pathway. Importantly, we identify a new strategy to target metastatic TNBC in vivo by repurposing FDA-approved potassium channel blockers. Our results provide an understanding of the mechanisms by which bioelectricity regulates cancer cell invasion and metastasis that could lead to a new class of therapeutics for patients with metastatic disease.

scholarly journals The matrix protein Fibulin-3 promotes KISS1R induced triple negative breast cancer cell invasion

Oncotarget ◽  
2018 ◽  
Vol 9 (53) ◽  
pp. 30034-30052 ◽  
Author(s):  
Michelle M. Noonan ◽  
Magdalena Dragan ◽  
Michael M. Mehta ◽  
David A. Hess ◽  
Muriel Brackstone ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Triple Negative Breast Cancer ◽  
Cell Invasion ◽  
Matrix Protein ◽  
Triple Negative ◽  
Cancer Cell Invasion ◽  
Breast Cancer Cell Invasion ◽  
The Matrix

scholarly journals TACE-dependent TGFα shedding drives triple-negative breast cancer cell invasion

2013 ◽  
pp. n/a-n/a ◽  
Author(s):  
Orsi Giricz ◽  
Veronica Calvo ◽  
Esther A. Peterson ◽  
Christiane M. Abouzeid ◽  
Paraic A. Kenny
Keyword(s):  
Breast Cancer ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Triple Negative Breast Cancer ◽  
Cell Invasion ◽  
Triple Negative ◽  
Cancer Cell Invasion ◽  
Breast Cancer Cell Invasion

GRB7 is required for triple-negative breast cancer cell invasion and survival

2011 ◽  
Vol 133 (2) ◽  
pp. 607-615 ◽  
Author(s):  
Orsi Giricz ◽  
Verónica Calvo ◽  
Stephanie C. Pero ◽  
David N. Krag ◽  
Joseph A. Sparano ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Triple Negative Breast Cancer ◽  
Cell Invasion ◽  
Triple Negative ◽  
Cancer Cell Invasion ◽  
Breast Cancer Cell Invasion

scholarly journals Receptor-Type Protein Tyrosine Phosphatase Alpha (PTPα) mediates MMP14 localization and facilitates triple-negative breast cancer cell invasion.

2021 ◽  
pp. mbc.E20-01-0060
Author(s):  
Lisa R. Decotret ◽  
Brennan J. Wadsworth ◽  
Ling Vicky Li ◽  
Chinten J. Lim ◽  
Kevin L. Bennewith ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Plasma Membrane ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Triple Negative Breast Cancer ◽  
Cell Invasion ◽  
Protein Tyrosine Phosphatase ◽  
Triple Negative ◽  
Tyrosine Phosphatase ◽  
Cancer Cell Invasion

The ability of cancer cells to invade into surrounding tissues requires degradation of the extracellular matrix (ECM). Invasive structures, such as invadopodia, form on the plasma membrane of cancer cells and secrete ECM-degrading proteases that play crucial roles in cancer cell invasion. We have previously shown that protein tyrosine phosphatase alpha (PTPα) regulates focal adhesion formation and migration of normal cells. Here we report a novel role for PTPα in promoting triple-negative breast cancer cell invasion in vitro and in vivo. We show that PTPα knockdown reduces ECM degradation and cellular invasion of MDA-MB-231 cells through Matrigel. PTPα is not a component of TKS5-positive structures resembling invadopodia; rather, PTPα localizes with endosomal structures positive for MMP14, caveolin-1, and early endosome antigen 1. Furthermore, PTPα regulates MMP14 localization to plasma membrane protrusions, suggesting a role for PTPα in intracellular trafficking of MMP14. Importantly, we show that orthotopic MDA-MB-231 tumours depleted of PTPα exhibit reduced invasion into the surrounding mammary fat pad. These findings suggest a novel role for PTPα in regulating the invasion of triple-negative breast cancer cells.

SASH1 suppresses triple-negative breast cancer cell invasion through YAP-ARHGAP42-actin axis

Oncogene ◽  
2020 ◽  
Vol 39 (27) ◽  
pp. 5015-5030
Author(s):  
Ke Jiang ◽  
Peng Liu ◽  
Huizhe Xu ◽  
Dapeng Liang ◽  
Kun Fang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Triple Negative Breast Cancer ◽  
Cell Invasion ◽  
Triple Negative ◽  
Cancer Cell Invasion ◽  
Breast Cancer Cell Invasion

scholarly journals Biomimetic oxygen delivery nanoparticles for enhancing photodynamic therapy in triple-negative breast cancer

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Hanyi Fang ◽  
Yongkang Gai ◽  
Sheng Wang ◽  
Qingyao Liu ◽  
Xiao Zhang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Photodynamic Therapy ◽  
Cancer Cell ◽  
Triple Negative Breast Cancer ◽  
Oxygen Delivery ◽  
Therapeutic Efficacy ◽  
Triple Negative ◽  
Oxygen Solubility ◽  
Post Injection

Abstract Background Triple-negative breast cancer (TNBC) is a kind of aggressive breast cancer with a high rate of metastasis, poor overall survival time, and a low response to targeted therapies. To improve the therapeutic efficacy and overcome the drug resistance of TNBC treatments, here we developed the cancer cell membrane-coated oxygen delivery nanoprobe, CCm–HSA–ICG–PFTBA, which can improve the hypoxia at tumor sites and enhance the therapeutic efficacy of the photodynamic therapy (PDT), resulting in relieving the tumor growth in TNBC xenografts. Results The size of the CCm–HSA–ICG–PFTBA was 131.3 ± 1.08 nm. The in vitro 1O2 and ROS concentrations of the CCm–HSA–ICG–PFTBA group were both significantly higher than those of the other groups (P < 0.001). In vivo fluorescence imaging revealed that the best time window was at 24 h post-injection of the CCm–HSA–ICG–PFTBA. Both in vivo 18F-FMISO PET imaging and ex vivo immunofluorescence staining results exhibited that the tumor hypoxia was significantly improved at 24 h post-injection of the CCm–HSA–ICG–PFTBA. For in vivo PDT treatment, the tumor volume and weight of the CCm–HSA–ICG–PFTBA with NIR group were both the smallest among all the groups and significantly decreased compared to the untreated group (P < 0.01). No obvious biotoxicity was observed by the injection of CCm–HSA–ICG–PFTBA till 14 days. Conclusions By using the high oxygen solubility of perfluorocarbon (PFC) and the homologous targeting ability of cancer cell membranes, CCm–HSA–ICG–PFTBA can target tumor tissues, mitigate the hypoxia of the tumor microenvironment, and enhance the PDT efficacy in TNBC xenografts. Furthermore, the HSA, ICG, and PFC are all FDA-approved materials, which render the nanoparticles highly biocompatible and enhance the potential for clinical translation in the treatment of TNBC patients.

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