Faculty Opinions recommendation of Gain Fat-Lose Metastasis: Converting Invasive Breast Cancer Cells into Adipocytes Inhibits Cancer Metastasis.

AbstractPhysical activity has been consistently linked to decreased incidence of breast cancer and a substantial increase in the length of survival of patients with breast cancer. However, the understanding of how applied physical forces directly regulate breast cancer remains limited. We investigated the role of mechanical forces in altering the chemoresistance, proliferation and metastasis of breast cancer cells. We found that applied mechanical tension can dramatically alter gene expression in breast cancer cells, leading to decreased proliferation, increased resistance to chemotherapeutic treatment and enhanced adhesion to inflamed endothelial cells and collagen I under fluidic shear stress. A mechanistic analysis of the pathways involved in these effects supported a complex signaling network that included Abl1, Lck, Jak2 and PI3K to regulate pro-survival signaling and enhancement of adhesion under flow. Studies using mouse xenograft models demonstrated reduced proliferation of breast cancer cells with orthotopic implantation and increased metastasis to the skull when the cancer cells were treated with mechanical load. Using high throughput mechanobiological screens we identified pathways that could be targeted to reduce the effects of load on metastasis and found that the effects of mechanical load on bone colonization could be reduced through treatment with a PI3Kγ inhibitor.

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A novel 3-D bio-microfluidic system mimicking in vivo heterogeneous tumour microstructures reveals complex tumour–stroma interactions

Lab on a Chip ◽

10.1039/c7lc00191f ◽

2017 ◽

Vol 17 (16) ◽

pp. 2852-2860 ◽

Cited By ~ 15

Author(s):

Qihui Fan ◽

Ruchuan Liu ◽

Yang Jiao ◽

Chunxiu Tian ◽

James D. Farrell ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Invasive Breast Cancer ◽

Stromal Cells ◽

Breast Cancer Cells ◽

Microfluidic System ◽

Tumour Stroma ◽

Collagen Hydrogel

A 3-D microfluidic system consisting of microchamber arrays embedded in a collagen hydrogel with tunable biochemical gradients was constructed for investigating interactions between invasive breast cancer cells and stromal cells.

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TLR4 Ligand/H2O2 Enhances TGF-β1 Signaling to Induce Metastatic Potential of Non-Invasive Breast Cancer Cells by Activating Non-Smad Pathways

PLoS ONE ◽

10.1371/journal.pone.0065906 ◽

2013 ◽

Vol 8 (5) ◽

pp. e65906 ◽

Cited By ~ 14

Author(s):

Yuan-Hong Zhou ◽

Sheng-Jun Liao ◽

Dong Li ◽

Jing Luo ◽

Jing-Jing Wei ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Invasive Breast Cancer ◽

Breast Cancer Cells ◽

Metastatic Potential ◽

Non Invasive ◽

Tlr4 Ligand ◽

Tgf Β1

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The Differential Distribution of RAPTA-T in Non-Invasive and Invasive Breast Cancer Cells Correlates with Its Anti-Invasive and Anti-Metastatic Effects

International Journal of Molecular Sciences ◽

10.3390/ijms18091869 ◽

2017 ◽

Vol 18 (9) ◽

pp. 1869 ◽

Cited By ~ 13

Author(s):

Ronald Lee ◽

Stéphane Escrig ◽

Catherine Maclachlan ◽

Graham Knott ◽

Anders Meibom ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Invasive Breast Cancer ◽

Breast Cancer Cells ◽

Differential Distribution ◽

Non Invasive

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Twist-mediated PAR1 induction is required for breast cancer progression and metastasis by inhibiting Hippo pathway

Cell Death and Disease ◽

10.1038/s41419-020-2725-4 ◽

2020 ◽

Vol 11 (7) ◽

Author(s):

Yifan Wang ◽

Ruocen Liao ◽

Xingyu Chen ◽

Xuhua Ying ◽

Guanping Chen ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Cancer Progression ◽

Invasive Breast Cancer ◽

Breast Cancer Cells ◽

Epithelial Mesenchymal Transition ◽

Hippo Pathway ◽

Breast Cancer Patients ◽

Mesenchymal Transition

Abstract Breast cancer is considered to be the most prevalent cancer in women worldwide, and metastasis is the primary cause of death. Protease-activated receptor 1 (PAR1) is a GPCR family member involved in the invasive and metastatic processes of cancer cells. However, the functions and underlying mechanisms of PAR1 in breast cancer remain unclear. In this study, we found that PAR1 is highly expressed in high invasive breast cancer cells, and predicts poor prognosis in ER-negative and high-grade breast cancer patients. Mechanistically, Twist transcriptionally induces PAR1 expression, leading to inhibition of Hippo pathway and activation of YAP/TAZ; Inhibition of PAR1 suppresses YAP/TAZ-induced epithelial-mesenchymal transition (EMT), invasion, migration, cancer stem cell (CSC)-like properties, tumor growth and metastasis of breast cancer cells in vitro and in vivo. These findings suggest that PAR1 acts as a direct transcriptionally target of Twist, can promote EMT, tumorigenicity and metastasis by controlling the Hippo pathway; this may lead to a potential therapeutic target for treating invasive breast cancer.

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