scholarly journals Post-transcriptional repression of circadian component CLOCK regulates cancer-stemness in murine breast cancer cells

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Takashi Ogino ◽  
Naoya Matsunaga ◽  
Takahiro Tanaka ◽  
Tomohito Tanihara ◽  
Hideki Terajima ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Transcriptional Repression ◽  
Aldh Activity ◽  
Invasive Potential ◽  
Cancer Treatments ◽  
Cancer Stemness ◽  
4T1 Cells ◽  
Novel Strategy ◽  
Post Transcriptional Regulation

Disruption of the circadian clock machinery in cancer cells is implicated in tumor malignancy. Studies on cancer therapy reveal the presence of heterogeneous cells, including breast cancer stem-like cells (BCSCs), in breast tumors. BCSCs are often characterized by high aldehyde dehydrogenase (ALDH) activity, associated with the malignancy of cancers. In this study, we demonstrated the negative regulation of ALDH activity by the major circadian component CLOCK in murine breast cancer 4T1 cells. The expression of CLOCK was repressed in high-ALDH-activity 4T1, and enhancement of CLOCK expression abrogated their stemness properties, such as tumorigenicity and invasive potential. Furthermore, reduced expression of CLOCK in high-ALDH-activity 4T1 was post-transcriptionally regulated by microRNA: miR-182. Knockout of miR-182 restored the expression of CLOCK, resulted in preventing tumor growth. Our findings suggest that increased expression of CLOCK in BCSCs by targeting post-transcriptional regulation overcame stemness-related malignancy and may be a novel strategy for breast cancer treatments.

scholarly journals Post-transcriptional repression of FOXO1 by QKI results in low levels of FOXO1 expression in breast cancer cells

2013 ◽  
Vol 31 (3) ◽  
pp. 1459-1465 ◽  
Author(s):  
FANG YU ◽  
LIANG JIN ◽  
GUODONG YANG ◽  
LIN JI ◽  
FENG WANG ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Transcriptional Repression ◽  
Breast Cancer Cells ◽  
Low Levels

scholarly journals Nuclear ErbB2 represses DEPTOR transcription to inhibit autophagy in breast cancer cells

2021 ◽  
Vol 12 (4) ◽  
Author(s):  
Yanli Bi ◽  
Longyuan Gong ◽  
Pengyuan Liu ◽  
Xiufang Xiong ◽  
Yongchao Zhao
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Transcriptional Repression ◽  
Breast Cancer Cells ◽  
Kinase Activity ◽  
Nuclear Translocation ◽  
Extracellular Signals ◽  
Consensus Binding Sequence ◽  
Binding Sequence

AbstractErbB2, a classical receptor tyrosine kinase, is frequently overexpressed in breast cancer cells. Although the role of ErbB2 in the transmission of extracellular signals to intracellular matrix has been widely studied, the functions of nuclear ErbB2 remain largely elusive. Here, we report a novel function of nuclear ErbB2 in repressing the transcription of DEPTOR, a direct inhibitor of mTOR. Nuclear ErbB2 directly binds to the consensus binding sequence in the DEPTOR promoter to repress its transcription. The kinase activity of ErbB2 is required for its nuclear translocation and transcriptional repression of DEPTOR. Moreover, the repressed DEPTOR by nuclear ErbB2 inhibits the induction of autophagy by activating mTORC1. Thus, our study reveals a novel mechanism for autophagy regulation by functional ErbB2, which translocates to the nucleus and acts as a transcriptional regulator to suppress DEPTOR transcription, leading to activation of the PI3K/AKT/mTOR pathway to inhibit autophagy.

scholarly journals N-Dihydrogalactochitosan Potentiates the Radiosensitivity of Liver Metastatic Tumor Cells Originated from Murine Breast Tumors

2019 ◽  
Vol 20 (22) ◽  
pp. 5581
Author(s):  
Chung-Yih Wang ◽  
Chun-Yuan Chang ◽  
Chun-Yu Wang ◽  
Kaili Liu ◽  
Chia-Yun Kang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Synergistic Effects ◽  
Metastatic Breast ◽  
Treatment Modalities ◽  
X Rays ◽  
Dna Breaks ◽  
4T1 Cells ◽  
4T1 Breast Cancer

Radiation is a widely used therapeutic method for treating breast cancer. N-dihydrogalactochitosan (GC), a biocompatible immunostimulant, is known to enhance the effects of various treatment modalities in different tumor types. However, whether GC can enhance the radiosensitivity of cancer cells remains to be explored. In this study, triple-negative murine 4T1 breast cancer cells transduced with multi-reporter genes were implanted in immunocompetent Balb/C mice to track, dissect, and identify liver-metastatic 4T1 cells. These cells expressed cancer stem cell (CSC) -related characteristics, including the ability to form spheroids, the expression of the CD44 marker, and the increase of protein stability. We then ex vivo investigated the potential effect of GC on the radiosensitivity of the liver-metastatic 4T1 breast cancer cells and compared the results to those of parental 4T1 cells subjected to the same treatment. The cells were irradiated with increased doses of X-rays with or without GC treatment. Colony formation assays were then performed to determine the survival fractions and radiosensitivity of these cells. We found that GC preferably increased the radiosensitivity of liver-metastatic 4T1 breast cancer cells rather than that of the parental cells. Additionally, the single-cell DNA electrophoresis assay (SCDEA) and γ-H2AX foci assay were performed to assess the level of double-stranded DNA breaks (DSBs). Compared to the parental cells, DNA damage was significantly increased in liver-metastatic 4T1 cells after they were treated with GC plus radiation. Further studies on apoptosis showed that this combination treatment increased the sub-G1 population of cells, but not caspase-3 cleavage, in liver-metastatic breast cancer cells. Taken together, the current data suggest that the synergistic effects of GC and irradiation might be used to enhance the efficacy of radiotherapy in treating metastatic tumors.

scholarly journals Intracellular Delivery of siRNAs Targeting AKT and ERBB2 Genes Enhances Chemosensitization of Breast Cancer Cells in a Culture and Animal Model

Pharmaceutics ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 458 ◽  
Author(s):  
Tahereh Fatemian ◽  
Hamid Reza Moghimi ◽  
Ezharul Hoque Chowdhury
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Pharmacokinetic Profile ◽  
Carbonate Apatite ◽  
Delivery Device ◽  
Synergistic Interactions ◽  
Anti Cancer ◽  
4T1 Cells

Pharmacotherapy as the mainstay in the management of breast cancer suffers from various drawbacks, including non-targeted biodistribution, narrow therapeutic and safety windows, and also resistance to treatment. Thus, alleviation of the constraints from the pharmacodynamic and pharmacokinetic profile of classical anti-cancer drugs could lead to improvements in efficacy and patient survival in malignancies. Moreover, modifications in the genetic pathophysiology of cancer via administration of small nucleic acids might pave the way towards higher response rates to chemotherapeutics. Inorganic pH-dependent carbonate apatite (CA) nanoparticles were utilized in this study to efficiently deliver various classes of therapeutics into cancer cells. Co-delivery of drugs and genetic materials was successfully attained through a carbonate apatite delivery device. On 4T1 cells, siRNAs against AKT and ERBB2 plus paclitaxel or docetaxel resulted in the largest increase in anti-cancer effects compared to CA/paclitaxel or CA/docetaxel. Therefore, these ingredients were selected for further in vivo investigations. Animals receiving injections of CA/paclitaxel or CA/docetaxel loaded with siRNAs against AKT and ERBB2 possessed significantly smaller tumors compared to CA/drug-treated mice. Interestingly, synergistic interactions in target protein knock down with combinations of CA/AKT/paclitaxel, CA/ERBB2/docetaxel were documented via western blotting.

scholarly journals Melatonin Does Not Alter Cell Proliferation in Metastatic Breast Cancer Cells

Proceedings ◽  
2018 ◽  
Vol 2 (25) ◽  
pp. 1567
Author(s):  
Gamze Tanriover ◽  
Sayra Dilmac ◽  
Nuray Erin
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Chemotherapeutic Agent ◽  
Metastatic Breast ◽  
Cancer Treatments ◽  
Anti Oxidant ◽  
New Treatment ◽  
Oxidant Effect

Breast cancer treatments continue to be investigated with supported by new treatment methods. Melatonin is a hormone that can be effective in the treatment of breast cancer due to its anti-oxidant effect. Melatonin had previously shown to inhibit proliferation of cancer cells. In this study, we aimed to determine the effect of melatonin on the proliferation of metastatic breast cancer cells in comparison to doxorubicin, a well-known chemotherapeutic agent. Doxorubicin inhibited proliferation of metastatic breast cancer cells while melatonin has no effect. We are currently examining the effects of melatonin and doxorubicin combination therapy on metastatic breast cancer cells.

scholarly journals Involvement of post-transcriptional regulation of FOXO1 by HuR in 5-FU-induced apoptosis in breast cancer cells

2013 ◽  
Vol 6 (1) ◽  
pp. 156-160 ◽  
Author(s):  
YUNBO LI ◽  
JINHAI YU ◽  
DANHUA DU ◽  
SHUANGLIN FU ◽  
YE CHEN ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Transcriptional Regulation ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Induced Apoptosis ◽  
Post Transcriptional Regulation

scholarly journals p14ARF Post-Transcriptional Regulation of Nuclear Cyclin D1 in MCF-7 Breast Cancer Cells: Discrimination between a Good and Bad Prognosis?

PLoS ONE ◽  
2012 ◽  
Vol 7 (7) ◽  
pp. e42246 ◽  
Author(s):  
Eileen M. McGowan ◽  
Nham Tran ◽  
Nikki Alling ◽  
Daniel Yagoub ◽  
Lisa M. Sedger ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Transcriptional Regulation ◽  
Cyclin D1 ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Post Transcriptional Regulation ◽  
Mcf 7

scholarly journals Suppression of cancer relapse and metastasis by inhibiting cancer stemness

2015 ◽  
Vol 112 (6) ◽  
pp. 1839-1844 ◽  
Author(s):  
Youzhi Li ◽  
Harry A. Rogoff ◽  
Sarah Keates ◽  
Yuan Gao ◽  
Sylaja Murikipudi ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Cancer Therapeutics ◽  
Therapeutic Approaches ◽  
Cancer Treatments ◽  
Cancer Stemness ◽  
Recurrent Cancer ◽  
Cancer Relapse ◽  
Novel Approach ◽  
Cancer Types ◽  
Tumor Types

Partial or even complete cancer regression can be achieved in some patients with current cancer treatments. However, such initial responses are almost always followed by relapse, with the recurrent cancer being resistant to further treatments. The discovery of therapeutic approaches that counteract relapse is, therefore, essential for advancing cancer medicine. Cancer cells are extremely heterogeneous, even in each individual patient, in terms of their malignant potential, drug sensitivity, and their potential to metastasize and cause relapse. Indeed, hypermalignant cancer cells, termed cancer stem cells or stemness-high cancer cells, that are highly tumorigenic and metastatic have been isolated from cancer patients with a variety of tumor types. Moreover, such stemness-high cancer cells are resistant to conventional chemotherapy and radiation. Here we show that BBI608, a small molecule identified by its ability to inhibit gene transcription driven by Stat3 and cancer stemness properties, can inhibit stemness gene expression and block spherogenesis of or kill stemness-high cancer cells isolated from a variety of cancer types. Moreover, cancer relapse and metastasis were effectively blocked by BBI608 in mice. These data demonstrate targeting cancer stemness as a novel approach to develop the next generation of cancer therapeutics to suppress cancer relapse and metastasis.

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