Suspension State Promotes Drug Resistance of Breast Tumor Cells by Inducing ABCC3 Overexpression

2019 ◽  
Vol 190 (2) ◽  
pp. 410-422
Author(s):  
Ya Wang ◽  
Xiaomei Zhang ◽  
Boyuan Zhao ◽  
Zhiling Xu ◽  
Yonggang Lv
Keyword(s):  
Drug Resistance ◽  
Tumor Cells ◽  
Breast Tumor ◽  
Breast Tumor Cells

scholarly journals HDAC6 Inhibitors Sensitize Claudin-high Breast Cancer Cells to Cysteine Depletion via Activation of PKCγ Signaling

2020 ◽  
Author(s):  
Tahiyat Alothaim ◽  
Morgan Charbonneau ◽  
Xiaohu Tang
Keyword(s):  
Breast Cancer ◽  
Drug Resistance ◽  
Cell Death ◽  
Tumor Cells ◽  
Breast Tumor ◽  
Zinc Homeostasis ◽  
Cancer Type ◽  
Library Screening ◽  
Compound Library ◽  
Breast Tumor Cells

Abstract IntroductionTriple-negative breast cancer (TNBC) is a highly malignant breast cancer type with poor prognosis and lacks effective therapy. TNBC is not responsive to targeted therapy for hormone receptors and often exhibit resistance to current chemotherapeutic agents. Targeting tumor metabolism is an emergent strategy to treat cancer. Therefore, identification of tumor metabolic deregulations and development of effective targeted therapies are urgently needed.MethodsWe performed the epigenetic compound library screening in claudin-high breast tumor cells and identified therapeutical sensitizers to overcome the drug resistance of targeted cysteine-dependence therapy. Gene expression profiling were generated to analyze signaling pathways induced by the combined tubacin and cysteine deprivation treatment. Specific inhibitors, shRNA, and CRISPR/Cas9 gene editing approaches were used to target cellular proteins HDAC6 and PKCγ and examine their roles in cell death. Cell viability, RT-qPCR, and Western blotting assays were performed in cysteine-independent tumor cells to examine the anticancer effects of combined tubacin and cysteine deprivation treatment. ResultsWe found that TNBC has differential death responses to cysteine deprivation and the cysteine-dependence of TNBC corelates with the expression levels of claudin genes in addition to the classical EMT markers. To overcome drug resistance in claudin-high/cysteine-independent breast tumor cells, HDAC6 inhibitors were identified by the epigenetic compound library screening as potent sensitizers that synergize with cysteine deprivation to eradicate cysteine-independent tumor cells. Unexpectedly, HDAC6 knockout did not recapitulate the HDAC6 inhibitors-mediated synthetic lethality, indicating that HDAC6 is not the actual target of HDAC6 inhibitors in this context. Transcriptomic profiling revealed that HDAC6 inhibitors synergizes with cysteine depletion to trigger a profound gene transcriptional program. Notably, a zinc-related gene response was observed to accompany with a prominent increase of labile zinc in cells during cell death. We further showed that activation of PKCγ signaling is required to interfere cellular zinc homeostasis and drive HDAC6 inhibitors-mediated cell death.ConclusionOur study demonstrated that HDAC6 inhibitors function as potent sensitizers to overcome the resistance of cysteine deprivation in claudin-high breast tumor cells. Identification of such sensitizers would make the targeted cysteine-dependence therapy applicable in various subtypes of breast cancer.

scholarly journals MicroRNAs as the critical regulators of Doxorubicin resistance in breast tumor cells

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Amir Sadra Zangouei ◽  
Maliheh Alimardani ◽  
Meysam Moghbeli
Keyword(s):  
Drug Resistance ◽  
Side Effects ◽  
Tumor Cells ◽  
Clinical Outcomes ◽  
Breast Tumor ◽  
Present Review ◽  
Multi Drug Resistance ◽  
Main Body ◽  
Breast Tumor Cells ◽  
Non Invasive

Abstract Background Chemotherapy is one of the most common treatment options for breast cancer (BC) patients. However, about half of the BC patients are chemotherapeutic resistant. Doxorubicin (DOX) is considered as one of the first line drugs in the treatment of BC patients whose function is negatively affected by multi drug resistance. Due to the severe side effects of DOX, it is very important to diagnose the DOX resistant BC patients. Therefore, assessment of molecular mechanisms involved in DOX resistance can improve the clinical outcomes in BC patients by introducing the novel therapeutic and diagnostic molecular markers. MicroRNAs (miRNAs) as members of the non-coding RNAs family have pivotal roles in various cellular processes including cell proliferation and apoptosis. Therefore, aberrant miRNAs functions and expressions can be associated with tumor progression, metastasis, and drug resistance. Moreover, due to miRNAs stability in body fluids, they can be considered as non-invasive diagnostic markers for the DOX response in BC patients. Main body In the present review, we have summarized all of the miRNAs that have been reported to be associated with DOX resistance in BC for the first time in the world. Conclusions Since, DOX has severe side effects; it is required to distinguish the non DOX-responders from responders to improve the clinical outcomes of BC patients. This review highlights the miRNAs as pivotal regulators of DOX resistance in breast tumor cells. Moreover, the present review paves the way of introducing a non-invasive panel of prediction markers for DOX response among BC patients.

Suspension state promotes extravasation of breast tumor cells by increasing integrin β1 expression

BIOCELL ◽  
2018 ◽  
Vol 42 (1) ◽  
pp. 17-24 ◽  
Author(s):  
B. Zhang ◽  
Y. Zhang ◽  
X. Zhang ◽  
Y. LV
Keyword(s):  
Tumor Cells ◽  
Breast Tumor ◽  
Integrin Β1 ◽  
Breast Tumor Cells

scholarly journals Productive Infection of Human Breast Cancer Cell Lines with Human Cytomegalovirus (HCMV)

Pathogens ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 641
Author(s):  
Kaitlin M. Branch ◽  
Erica C. Garcia ◽  
Yin Maggie Chen ◽  
Matthew McGregor ◽  
Mikayla Min ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Breast Tumor ◽  
Cancer Cell Lines ◽  
Breast Cancer Cell Lines ◽  
Human Breast ◽  
Breast Tumor Cells

Breast cancer is the leading cause of cancer deaths among women worldwide. There are many known risk factors for breast cancer, but the role of infectious disease remains unclear. Human cytomegalovirus (HCMV) is a widespread herpesvirus that usually causes little disease. Because HCMV has been detected in breast tumor biopsy samples and is frequently transmitted via human breast milk, we investigated HCMV replication in breast tumor cells. Four human breast cancer cell lines with different expression profiles for the key diagnostic markers of the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2), were infected with a bacterial artificial chromosome-derived HCMV clinical strain TB40/E tagged with green fluorescent protein (GFP). Fluorescence microscopy confirmed that all four breast cancer cell lines supported virus entry. RNA was isolated from infected cells and the expression of immediate early (UL123), early (UL54), and late (UL111A) genes was confirmed using PCR. Viral proteins were detected by immunoblotting, and viral progeny were produced during the infection of breast tumor cells, as evidenced by subsequent infection of fibroblasts with culture supernatants. These results demonstrate that breast tumor cells support productive HCMV infection and could indicate that HCMV replication may play a role in breast cancer progression.

Synthetic Progestins in Breast Tumor Cells.

1993 ◽  
Vol 684 (1 Zinc-Finger P) ◽  
pp. 220-221
Author(s):  
ERIC KALKHOVEN ◽  
LINDA KWAKKENBOS-ISBRÜCKER ◽  
SIEGFRIED W. LAAT ◽  
BART BURG
Keyword(s):  
Tumor Cells ◽  
Breast Tumor ◽  
Breast Tumor Cells
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