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Article
STAT3 protects hematopoietic stem cells by preventing activation of a deleterious autocrine type-I interferon response
Hematopoietic stem and progenitor cells (HSPCs) maintain blood-forming and immune activity, yet intrinsic regulators of HSPCs remain elusive. STAT3 function in HSPCs has been difficult to dissect as Stat3-deficie...
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Article
Open AccessCell cycle arrest induces lipid droplet formation and confers ferroptosis resistance
How cells coordinate cell cycling with cell survival and death remains incompletely understood. Here, we show that cell cycle arrest has a potent suppressive effect on ferroptosis, a form of regulated cell dea...
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Article
Low-molecular-weight cyclin E deregulates DNA replication and damage repair to promote genomic instability in breast cancer
Low-molecular-weight cyclin E (LMW-E) is an N-terminus deleted (40 amino acid) form of cyclin E detected in breast cancer, but not in normal cells or tissues. LMW-E overexpression predicts poor survival in bre...
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Article
Open AccessLMW cyclin E and its novel catalytic partner CDK5 are therapeutic targets and prognostic biomarkers in salivary gland cancers
Salivary gland cancers (SGCs) are rare yet aggressive malignancies with significant histological heterogeneity, which has made prediction of prognosis and development of targeted therapies challenging. In majo...
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Article
Open AccessSpecific, reversible G1 arrest by UCN-01 in vivo provides cytostatic protection of normal cells against cytotoxic chemotherapy in breast cancer
Low-dose UCN-01 mediates G1 arrest in normal proliferating cell lines with an intact G1 to S transition but not tumour cells with a deregulated G1 to S checkpoint. Here we hypothesised that UCN-01 is effective...
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Article
Open AccessHistone modification profiling in breast cancer cell lines highlights commonalities and differences among subtypes
Epigenetic regulators are frequently mutated or aberrantly expressed in a variety of cancers, leading to altered transcription states that result in changes in cell identity, behavior, and response to therapy.
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Article
Inhibiting CDK in Cancer Therapy: Current Evidence and Future Directions
Cell cycle dysregulation is a hallmark of all cancers, resulting in uncontrolled proliferation. Cyclin dependent kinases (CDKs), a family of proteins that are involved in the regulation of the cell cycle, are ...
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Article
Open AccessCDK4/6 and autophagy inhibitors synergistically induce senescence in Rb positive cytoplasmic cyclin E negative cancers
Deregulation of the cell cycle machinery is a hallmark of cancer. While CDK4/6 inhibitors are FDA approved (palbociclib) for treating advanced estrogen receptor-positive breast cancer, two major clinical chall...
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Reference Work Entry In depth
Staurosporine
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Article
Open AccessPAF-Wnt signaling-induced cell plasticity is required for maintenance of breast cancer cell stemness
Cancer stem cells (CSCs) contribute to tumour heterogeneity, therapy resistance and metastasis. However, the regulatory mechanisms of cancer cell stemness remain elusive. Here we identify PCNA-associated facto...
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Article
A phase 1 study with dose expansion of the CDK inhibitor dinaciclib (SCH 727965) in combination with epirubicin in patients with metastatic triple negative breast cancer
Purpose, Low molecular weight cyclin E (LMW-E) isoforms, overexpressed in a majority (~70 %) of triple-negative breast cancers (TNBC), were found in preclinical models to mediate tumorige...
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Article
Open AccessErratum to: Elafin is downregulated during breast and ovarian tumorigenesis but its residual expression predicts recurrence
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Living Reference Work Entry In depth
Staurosporine
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Article
Open AccessElafin is downregulated during breast and ovarian tumorigenesis but its residual expression predicts recurrence
Elafin is an endogenous serine protease inhibitor. The majority of breast cancer cell lines lack elafin expression compared to human mammary epithelial cells. In this study, we hypothesized that elafin is down...
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Article
2′-OMe-phosphorodithioate-modified siRNAs show increased loading into the RISC complex and enhanced anti-tumour activity
Improving small interfering RNA (siRNA) efficacy in target cell populations remains a challenge to its clinical implementation. Here, we report a chemical modification, consisting of phosphorodithioate (PS2) a...
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Article
Open AccessElafin, an inhibitor of elastase, is a prognostic indicator in breast cancer
Elafin is an elastase-specific inhibitor with increased transcription in normal mammary epithelial cells compared to mammary carcinoma cells. In this report, we test the hypothesis that inhibition of elastase,...
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Article
Targeting low molecular weight cyclin E (LMW-E) in breast cancer
Low molecular weight cyclin E (LMW-E) plays an important oncogenic role in breast cancer. LMW-E, which is not found in normal tissue, can promote the formation of aggressive tumors and can lead to increased ge...
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Article
Semi-high throughput method of measuring proteasome inhibition in vitro and in cultured cells
The ubiquitin proteasome–proteolytic pathway has emerged as one of the most significant pathways in modulating protein homeostasis under both normal and disease states. The use of proteasome inhibitors (PI) ha...
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Reference Work Entry In depth
Staurosporine
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Article
Cyclin E deregulation is an early event in the development of breast cancer
Cyclin E has been shown to be overexpressed in some human breast cancers, however, data to support deregulation of cyclin E as an early event in human mammary tumor development is lacking. We analyzed surgical...
