scholarly journals JFK Is a Hypoxia-Inducible Gene That Functions to Promote Breast Carcinogenesis

2021 ◽  
Vol 9 ◽  
Author(s):  
Ziran Yang ◽  
Xuehong Zhou ◽  
Enrun Zheng ◽  
Yizhou Wang ◽  
Xinhua Liu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Mrna Level ◽  
Hypoxia Inducible Factor ◽  
Hypoxic Conditions ◽  
Important Player ◽  
Chemotherapeutic Treatment ◽  
Cancer Intervention ◽  
F Box Protein

Many carcinomas feature hypoxia, a condition has long been associated with tumor progression and poor prognosis, as well as resistance to chemoradiotherapy. Here, we report that the F-box protein JFK promotes mammary tumor initiation and progression in MMTV-PyMT murine model of spontaneous breast cancer. We find that JFK is inducible under hypoxic conditions, in which hypoxia-inducible factor HIF-1α binds to and transcriptionally activates JFK in breast cancer cells. Consistently, analysis of public clinical datasets reveals that the mRNA level of JFK is positively correlated with that of HIF-1α in breast cancer. We show that JFK deficiency leads to a decrease in HIF-1α-induced glycolysis in breast cancer and sensitizes hypoxic breast cancer cells to ionizing radiation and chemotherapeutic treatment. These results indicate that JFK is an important player in hypoxic response, supporting the pursuit of JFK as a potential therapeutic target for breast cancer intervention.

scholarly journals Cannabidiol Suppresses Angiogenesis and Stemness of Breast Cancer Cells by Downregulation of Hypoxia-Inducible Factors-1α

Cancers ◽  
2021 ◽  
Vol 13 (22) ◽  
pp. 5667
Author(s):  
Min Jee Jo ◽  
Bu Gyeom Kim ◽  
Woo Young Kim ◽  
Dae-Hee Lee ◽  
Hye Kyeong Yun ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Mrna Level ◽  
Recurrent Breast Cancer ◽  
Tube Formation ◽  
Angiogenic Potential ◽  
Von Hippel Lindau ◽  
Hypoxic Conditions ◽  
Recurrent Breast

To assess the effect of Cannabidiol (CBD) on the angiogenesis and stemness of breast cancer cells as well as proliferation. Methods: mRNA level and the amount of protein of vascular endothelial growth factor (VEGF) were determined by qRT-PCR and ELISA. The angiogenic potential of breast cancer cells under hypoxic conditions was identified by the HUVEC tube formation assay. The degradation of HIF-1α by CBD and the Src/von Hippel–Lindau tumor suppressor protein (VHL) interaction were assessed by a co-immunoprecipitation assay and Western blotting. To identify the stemness of mamospheres, they were evaluated by the sphere-forming assay and flow cytometry. Results: CBD can suppress angiogenesis and stem cell-like properties of breast cancer through Src/VHL/HIF-1α signaling. CBD may potentially be utilized in the treatment of refractory or recurrent breast cancer.

scholarly journals Biomechanical regulation of breast cancer metastasis and progression

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Adrianne Spencer ◽  
Andrew D. Sligar ◽  
Daniel Chavarria ◽  
Jason Lee ◽  
Darshil Choksi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Cancer Metastasis ◽  
Mechanical Load ◽  
Breast Cancer Metastasis ◽  
Proliferation And Metastasis ◽  
Xenograft Models ◽  
Chemotherapeutic Treatment ◽  
Complex Signaling

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.

Luteolin-Loading Her-2 Nanospheres Enhances Targeting and Therapeutic Effects of Breast Cancer

2021 ◽  
Vol 17 (8) ◽  
pp. 1545-1553
Author(s):  
Chuanguang Xiao ◽  
Xiaohong Wang ◽  
Jiacheng Shen ◽  
Yanjie Xia ◽  
Shusheng Qiu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Water Solubility ◽  
Ultrasonic Method ◽  
Mrna Level ◽  
Therapeutic Effects ◽  
Treatment Benefit ◽  
Protein Levels ◽  
Her 2

Despite the broad anticancer activity, whereas the clinical application of luteolin is hindered by unsatisfactory water solubility and non-targeting. Herein, targeted inhibitory effects of luteolin-loading HER2 nanospheres (Her-2-NPs) were successfully prepared by thin film ultrasonic method. In comparison with the non-targeted nanospheres, Her-2 nanospheres could significantly boost the intake of luteolin in SK-BR-3 cells. The proliferation and apoptosis of breast cancer cells were detected by MTT testing and flow cytometry examination, respectively. Consequently, the expressions of FOXO1 mRNA level was detected using qPCR assay and protein level was detected using Westernblot. We discovered that Luteolin-loading Her-2 nanospheres could significantly hinder the proliferation of breast cancer cells, down-regulation their migration, and up-regulation FOXO1 expression at mRNA and protein levels, reveal a mechanism whereby luteolin interferes with breast cancer. Collectively, these results suggest Her-2-modified nanospheres increases the efficiency of luteolin uptake and thus improves the treatment benefit of breast cancer.

scholarly journals Toll-Iike Receptor-3 Activation Enhances Malignant Traits in Human Breast Cancer Cells Through Hypoxia-inducible Factor-1α

2020 ◽  
Vol 40 (10) ◽  
pp. 5379-5391
Author(s):  
FRANCESCA SCATOZZA ◽  
ANTONELLA D'AMORE ◽  
ROSARIA ANNA FONTANELLA ◽  
PAOLA DE CESARIS ◽  
FRANCESCO MARAMPON ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Human Breast Cancer ◽  
Breast Cancer Cells ◽  
Hypoxia Inducible Factor ◽  
Human Breast Cancer Cells ◽  
Human Breast ◽  
Hypoxia Inducible Factor 1Α

scholarly journals Overexpression of MMP-9 and HIF-1α in Breast Cancer Cells under Hypoxic Conditions

2011 ◽  
Vol 14 (2) ◽  
pp. 88 ◽  
Author(s):  
Jae Young Choi ◽  
Yeon Soo Jang ◽  
Sun Young Min ◽  
Jeong Yoon Song
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Hypoxic Conditions

scholarly journals The G Protein-coupled Receptor 30 Is Up-regulated by Hypoxia-inducible Factor-1α (HIF-1α) in Breast Cancer Cells and Cardiomyocytes

2011 ◽  
Vol 286 (12) ◽  
pp. 10773-10782 ◽  
Author(s):  
Anna Grazia Recchia ◽  
Ernestina Marianna De Francesco ◽  
Adele Vivacqua ◽  
Diego Sisci ◽  
Maria Luisa Panno ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Hypoxia Inducible Factor ◽  
Low Oxygen ◽  
Downstream Target ◽  
Adaptive Mechanisms ◽  
Cancer Tissues ◽  
Apoptotic Effects ◽  
G Protein Coupled

GPR30, also known as GPER, has been suggested to mediate rapid effects induced by estrogens in diverse normal and cancer tissues. Hypoxia is a common feature of solid tumors involved in apoptosis, cell survival, and proliferation. The response to low oxygen environment is mainly mediated by the hypoxia-inducible factor named HIF-1α, which activates signaling pathways leading to adaptive mechanisms in tumor cells. Here, we demonstrate that the hypoxia induces HIF-1α expression, which in turn mediates the up-regulation of GPER and its downstream target CTGF in estrogen receptor-negative SkBr3 breast cancer cells and in HL-1 cardiomyocytes. Moreover, we show that HIF-1α-responsive elements located within the promoter region of GPER are involved in hypoxia-dependent transcription of GPER, which requires the ROS-induced activation of EGFR/ERK signaling in both SkBr3 and HL-1 and cells. Interestingly, the apoptotic response to hypoxia was prevented by estrogens through GPER in SkBr3 cells. Taken together, our data suggest that the hypoxia-induced expression of GPER may be included among the mechanisms involved in the anti-apoptotic effects elicited by estrogens, particularly in a low oxygen microenvironment.

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