scholarly journals Genetic depletion and pharmacological targeting of αv integrin in breast cancer cells impairs metastasis in zebrafish and mouse xenograft models

2015 ◽  
Vol 17 (1) ◽  
Author(s):  
Yihao Li ◽  
Yvette Drabsch ◽  
Philippe Pujuguet ◽  
Jiang Ren ◽  
Theo van Laar ◽  
...  
2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Adrianne Spencer ◽  
Andrew D. Sligar ◽  
Daniel Chavarria ◽  
Jason Lee ◽  
Darshil Choksi ◽  
...  

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.


2018 ◽  
Vol 19 (1) ◽  
pp. 74-80 ◽  
Author(s):  
Peng Liu ◽  
Hailin Tang ◽  
Jiali Wu ◽  
Xingsheng Qiu ◽  
Yanan Kong ◽  
...  

Background: Long non-coding RNAs play crucial roles in various biological activities and diseases. The role of long intergenic non-coding RNA01638 (linc01638) in breast cancer, especially in HER2-positive breast cancer, remains largely unknown. Objective: To investigate the effect of linc01638 on tumorigenesis in HER2-positive breast cancer. </P><P> Methods: We first used qRT-PCR to detect linc01638 expression in HER2-positive breast cancer cells and tissues. Then we analyzed the effects of linc01638 expression in HER2-positive breast cancer cells through cell apoptosis assay, cell proliferation assay, colony formation assay, and cell invasion assay. We conducted mouse xenograft model to further confirm the role of linc01638 in HER2-positive breast cancer. Moreover, we used Western blot and IHC analysis to access the effect of linc01638 on DNMTs, BRCA1 and PTEN expressions in transplanted tumors. Results: Linc01638 was found to be remarkably overexpressed in HER2-positive breast cancer cells and tissues. Suppression of linc01638 enhanced cell apoptosis, as well as inhibited the growth and invasiveness of HER2-positive breast cancer cells in vitro and tumor progression and metastasis in vivo. Furthermore, inhibition of linc01638 by shRNA attenuated expression of DNMT1, DNMT3a, and DNMT3b, and promoted expression of BRCA1 and PTEN in HER2-positive breast cancer cells and mouse xenograft models. Linc01638 might be a promising biomarker and therapeutic target for treatment of HER2-positive breast cancer.


2008 ◽  
Vol 68 (14) ◽  
pp. 5529-5532 ◽  
Author(s):  
Jean-Pierre Eliane ◽  
Madeline Repollet ◽  
Kathryn E. Luker ◽  
Martha Brown ◽  
James M. Rae ◽  
...  

2020 ◽  
Author(s):  
Adrianne Spencer ◽  
Andrew D. Sligar ◽  
Daniel Chavarria ◽  
Jason Lee ◽  
Darshil Choksi ◽  
...  

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.


2021 ◽  
Vol 21 ◽  
Author(s):  
Chuansheng Yang ◽  
Hongbo Zhu ◽  
Yeru Tan ◽  
Renjie Zhu ◽  
Xiaoping Wu ◽  
...  

Background: The function of MALAT1, a kind of long non-coding RNAs (lncRNA), in HER2-positive breast cancer remains largely unexplored. Therefore, there is a need investigate the effect of MALAT1 on tumor development in HER2-positive breast cancer. Objectives: We detected MALAT1 expression in HER2-positive breast cancer cells and tissues and analyzed the effects of MALAT1 on cell proliferation in HER2-positive breast cancer cell lines (BT-474 and SKBR3). Methods: A mouse xenograft model was established for detecting the function of MALAT1 in HER2-positive breast cancer. Results amp; Discussion: As a result, MALAT1 was remarkably up-regulated in HER2-positive breast cancer both in cells and tissues. In addition, the silence of MALAT1 inhibited the proliferation of HER2-positive breast cancer cells both in vitro and in vivo. Furthermore, the knockdown of MALAT1 by shRNA down-regulated DNMT1, DNMT3a, and DNMT3b, while up-regulated BRCA1 and PTEN in HER2-positive breast cancer both in cell lines and mouse xenograft models. Conclusion: In short, MALAT1 might be a potential biomarker and therapeutic target for HER2-positive breast cancer therapy.


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