scholarly journals The Importance of Autophagy Regulation in Breast Cancer Development and Treatment

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Joanna Magdalena Zarzynska
Keyword(s):  
Breast Cancer ◽  
Cell Growth ◽  
Malignant Tumor ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Cell Stress ◽  
Cancer Development ◽  
Cancer Initiation ◽  
Life Threatening

Breast cancer (BC) is a potentially life-threatening malignant tumor that still causes high mortality among women. One of the mechanisms through which cancer development could be controlled is autophagy. This process exerts different effects during the stages of cancer initiation and progression due to the occurring superimposition of signaling pathways of autophagy and carcinogenesis. Chronic inhibition of autophagy or autophagy deficiency promotes cancer, due to instability of the genome and defective cell growth and as a result of cell stress. However, increased induction of autophagy can become a mechanism which allows tumor cells to survive the conditions of hypoxia, acidosis, or chemotherapy. Therefore, in the development of cancer, autophagy is regarded as a double-edged sword. Determination of the molecular mechanisms underlying autophagy regulation and its role in tumorigenesis is an essential component of modern anticancer strategies. Results of scientific studies show that inhibition of autophagy may enhance the effectiveness of currently used anticancer drugs and other therapies (like radiotherapy). However, in some cases, the promotion of autophagy can induce death and, hence, elimination of the cancer cells and reduction of tumor size. This review summarizes the current knowledge on autophagy regulation in BC and up-to-date anticancer strategies correlated with autophagy.

scholarly journals RASSF1A Suppresses Estrogen-Dependent Breast Cancer Cell Growth through Inhibition of the Yes-Associated Protein 1 (YAP1), Inhibition of the Forkhead Box Protein M1 (FOXM1), and Activation of Forkhead Box Transcription Factor 3A (FOXO3A)

Cancers ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2689
Author(s):  
Sven Roßwag ◽  
Gitta Thiede ◽  
Jonathan P. Sleeman ◽  
Sonja Thaler
Keyword(s):  
Breast Cancer ◽  
Transcription Factor ◽  
Cell Growth ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Cancer Cell Growth ◽  
Breast Cancer Cell Growth ◽  
Forkhead Box ◽  
Cancer Initiation ◽  
And Function

The estrogen receptor alpha (ERα) is expressed by the majority of breast cancers and plays an important role in breast cancer development and tumor outgrowth. Although ERα is well known to be a specific and efficient therapeutic target, the molecular mechanisms that are responsible for the control of ERα expression and function in the context of breast cancer initiation and progression are complex and not completely elucidated. In previous work, we have demonstrated that the tumor suppressor RASSF1A inhibits ERα expression and function in ERα-positive breast cancer cells through an AKT-dependent mechanism. Transcriptional activators such as forkhead box protein M1 (FOXM1) and forkhead transcription factor 3A (FOXO3A) and signaling pathways such as the Hippo pathway are also known to modulate ERα expression and activity. Here we report that RASSF1A acts as an inhibitor of ERα-driven breast cancer cell growth through a complex, hierarchically organized network that initially involves suppression of the Hippo effector Yes-associated protein 1 (YAP1), which is followed by inhibition of AKT1 activity, increased FOXO3A activity as well as a blockade of FOXM1 and ERα expression. Together our findings provide important new mechanistic insights into how the loss of RASSF1A contributes to ERα+ breast cancer initiation and progression.

scholarly journals The oxytocin receptor signalling system and breast cancer: a critical review

Oncogene ◽  
2020 ◽  
Vol 39 (37) ◽  
pp. 5917-5932 ◽  
Author(s):  
Huiping Liu ◽  
Christian W. Gruber ◽  
Paul F. Alewood ◽  
Andreas Möller ◽  
Markus Muttenthaler
Keyword(s):  
Breast Cancer ◽  
Current Knowledge ◽  
Oxytocin Receptor ◽  
Cancer Development ◽  
Breast Cancer Cell Lines ◽  
Maternal Behaviour ◽  
Supporting Evidence ◽  
Breast Cancer Development ◽  
Signalling System ◽  
Cancer Management

Abstract Breast cancer is making up one-quarter of all new female cancer cases diagnosed worldwide. Breast cancer surgeries, radiation therapies, cytotoxic chemotherapies and targeted therapies have made significant progress and play a dominant role in breast cancer patient management. However, many challenges remain, including resistance to systemic therapies, tumour recurrence and metastasis. The cyclic neuropeptide oxytocin (OT) elicits a plethora of biological responses via the oxytocin receptor (OTR) in both the central and peripheral nervous system, including social bonding, stress, maternal behaviour, sexual activity, uterus contraction, milk ejection and cancer. As a typical member of the G protein-coupled receptor family, OTR represents also an intriguing target for cancer therapy. There is emerging evidence that OTR plays a role in breast cancer development and progression, and several breast cancer cell lines express OTR. However, despite supporting evidence that OT lowers breast cancer risks, its mechanistic role in breast cancer development and the related signalling pathways are not fully understood. Here, we review the current knowledge of the OT/OTR signalling system in healthy breast tissue as well as in breast cancer, and discuss OTR as a potential therapeutic target for breast cancer management.

scholarly journals Two Faces of TGF-Beta1 in Breast Cancer

2014 ◽  
Vol 2014 ◽  
pp. 1-16 ◽  
Author(s):  
Joanna Magdalena Zarzynska
Keyword(s):  
Breast Cancer ◽  
Cell Cycle Progression ◽  
Epithelial To Mesenchymal Transition ◽  
Current Knowledge ◽  
Clinical Investigation ◽  
Mesenchymal Transition ◽  
Early Stages ◽  
New Therapeutic Approaches ◽  
Genes Encoding ◽  
Life Threatening

Breast cancer (BC) is potentially life-threatening malignancy that still causes high mortality among women. Scientific research in this field is focused on deeper understanding of pathogenesis and progressing of BC, in order to develop relevant diagnosis and improve therapeutic treatment. Multifunctional cytokine TGF-β1 is one of many factors that have a direct influence on BC pathophysiology. Expression of TGF-β1, induction of canonical and noncanonical signaling pathways, and mutations in genes encoding TGF-β1 and its receptors are correlated with oncogenic activity of this cytokine. In early stages of BC this cytokine inhibits epithelial cell cycle progression and promotes apoptosis, showing tumor suppressive effects. However, in late stages, TGF-β1 is linked with increased tumor progression, higher cell motility, cancer invasiveness, and metastasis. It is also involved in cancer microenvironment modification and promotion of epithelial to mesenchymal transition (EMT). This review summarizes the current knowledge on the phenomenon called “TGF-β1 paradox”, showing that better understanding of TGF-β1 functions can be a step towards development of new therapeutic approaches. According to current knowledge several drugs against TGF-β1 have been developed and are either in nonclinical or in early stages of clinical investigation.

scholarly journals A novel chemical inhibitor suppresses breast cancer cell growth and metastasis through inhibiting HPIP oncoprotein

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Pengyun Li ◽  
Shengjie Cao ◽  
Yubing Huang ◽  
Yanan Zhang ◽  
Jie Liu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Cell Growth ◽  
Cancer Therapy ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Cancer Development ◽  
Cancer Cell Growth ◽  
Breast Cancer Cell Growth ◽  
Anticancer Effects

AbstractIncreasing evidence suggests the pivotal role of hematopoietic pre-B-cell leukemia transcription factor (PBX)-interacting protein (HPIP/PBXIP1) in cancer development and progression, indicating that HPIP inhibition may be a promising target for cancer therapy. Here, we screened compounds inhibiting breast cancer cell proliferation with HPIP fused with green fluorescent protein as a reporter. A novel agent named TXX-1-10 derived from rimonabant, an antagonist of cannabinoid receptor 1 with anticancer effects, has been discovered to reduce HPIP expression and has greater inhibitory effects on breast cancer cell growth and metastasis in vitro and in vivo than rimonabant. TXX-1-10 regulates HPIP downstream targets, including several important kinases involved in cancer development and progression (e.g., AKT, ERK1/2, and FAK) as well as cell cycle-, apoptosis-, migration-, and epithelial-to-mesenchymal transition (EMT)-related genes. Consistent with the results of anticancer effects, genome-wide RNA sequencing indicated that TXX-1-10 has more significant effects on regulation of the expression of genes related to DNA replication, cell cycle, apoptosis, cell adhesion, cell migration, and invasion than rimonabant. In addition, TXX-1-10 significantly regulated genes associated with the cell growth and extracellular matrix organization, many of which were shown to be regulated by HPIP. Moreover, compared with rimonabant, TXX-1-10 greatly reduces blood-brain barrier penetrability to avoid adverse central depressive effects. These findings suggest that HPIP inhibition may be a useful strategy for cancer treatment and TXX-1-10 is a promising candidate drug for cancer therapy.

scholarly journals The Reactive Carbonyl Derivatives of Proteins, Methylglyoxal, and Malondialdehyde in Blood of Women with Breast Cancer

2021 ◽  
Vol 9 (B) ◽  
pp. 509-514
Author(s):  
Sabina Zhumakayeva ◽  
Larissa Muravlyova ◽  
Valentina Sirota ◽  
Vilen Molotov-Luchansky ◽  
Ryszhan Bakirova ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Molecular Mechanisms ◽  
Pathological Process ◽  
Carbonyl Derivatives ◽  
Mechanisms Of Carcinogenesis ◽  
High Cytotoxicity ◽  
Derivatives Of ◽  
Sensitive Marker ◽  
Literature Data Analysis

BACKGROUND: Every year 1.5 million women in the world are diagnosed with breast cancer (BC). In 2018, more than 260,000 new cases of cancer and more than 40,000 deaths due to this disease were detected. At the same time, in Kazakhstan, an intensive indicator of the incidences of BC in 2018 amounted to 25.3% per population of 100 thousand people (2017–24.5%) with a growth rate of 3.1%, which in absolute numbers are 4,648 new cases per year. In terms of mortality, BC ranks third after lung and stomach cancer (6.8%). AIM: This necessitates a detailed study of the molecular mechanisms that underlie the development and progression of BC. One of the mechanisms of carcinogenesis is oxidative stress (OS). An increase in malondialdehyde (MDA) levels was detected in the early stages of cancer. It was suggested that MDA, due to its high cytotoxicity, acts as a promoter of the tumor and cocarcinogen agent. METHODS: Therefore, violation of the parameters of OS in BC is in no doubt. However, according to the literature data analysis, these results are ambiguous and contradictory. There are no studies on a comprehensive assessment of the oxidative destruction of lipids, proteins, and nucleic acids in BC. CONCLUSION: The nature and direction of changes in various components of OS in patients with BC have not been adequately studied, which is necessary for a correct assessment of the involvement of OS in the mechanism of the pathological process and determination of a sensitive marker of the risk of BC or its progression.

scholarly journals Mechanisms of Resistance to CDK4/6 Inhibitors in Breast Cancer and Potential Biomarkers of Response

Breast Care ◽  
2017 ◽  
Vol 12 (5) ◽  
pp. 304-308 ◽  
Author(s):  
Cristina Guarducci ◽  
Martina Bonechi ◽  
Giulia Boccalini ◽  
Matteo Benelli ◽  
Emanuela Risi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Molecular Mechanisms ◽  
Randomized Clinical Trials ◽  
De Novo ◽  
Current Knowledge ◽  
Acquired Resistance ◽  
Metastatic Breast ◽  
Molecular Alterations ◽  
Potential Biomarkers

Randomized clinical trials demonstrated that CDK4/6 inhibitors are highly effective in patients with hormone receptor-positive (HR+), HER2-negative (HER2-) metastatic breast cancer in combination with endocrine therapy. The use of CDK4/6 inhibitors in clinics is becoming common for patients with HR+/HER2- metastatic breast cancer and will certainly increase in the near future. However, patients might show de novo or acquired resistance to these drugs. Molecular alterations have been suggested as determinants for de novo resistance to CDK4/6 inhibitors, but have never been validated in a clinical setting. In addition, molecular mechanisms of acquired resistance to palbociclib have been analyzed only in preclinical studies. Here we review the current knowledge on the available preclinical data about the mechanisms of de novo and acquired resistance to CDK4/6 inhibitors in breast cancer, and clinical data about potential biomarkers of response.

scholarly journals Cancer Initiation, Progression and Resistance: Are Phytocannabinoids from Cannabis sativa L. Promising Compounds?

Molecules ◽  
2021 ◽  
Vol 26 (9) ◽  
pp. 2668
Author(s):  
Ersilia Nigro ◽  
Marialuisa Formato ◽  
Giuseppina Crescente ◽  
Aurora Daniele
Keyword(s):  
Molecular Mechanisms ◽  
Cannabinoid Receptors ◽  
Cannabis Sativa ◽  
Current Knowledge ◽  
Endocannabinoid System ◽  
Peripheral Tissues ◽  
Positive Effects ◽  
Cancer Initiation

Cannabis sativa L. is a source of over 150 active compounds known as phytocannabinoids that are receiving renewed interest due to their diverse pharmacologic activities. Indeed, phytocannabinoids mimic the endogenous bioactive endocannabinoids effects through activation of CB1 and CB2 receptors widely described in the central nervous system and peripheral tissues. All phytocannabinoids have been studied for their protective actions towards different biological mechanisms, including inflammation, immune response, oxidative stress that, altogether, result in an inhibitory activity against the carcinogenesis. The role of the endocannabinoid system is not yet completely clear in cancer, but several studies indicate that cannabinoid receptors and endogenous ligands are overexpressed in different tumor tissues. Recently, in vitro and in vivo evidence support the effectiveness of phytocannabinoids against various cancer types, in terms of proliferation, metastasis, and angiogenesis, actions partially due to their ability to regulate signaling pathways critical for cell growth and survival. The aim of this review was to report the current knowledge about the action of phytocannabinoids from Cannabis sativa L. against cancer initiation and progression with a specific regard to brain, breast, colorectal, and lung cancer as well as their possible use in the therapies. We will also report the known molecular mechanisms responsible for such positive effects. Finally, we will describe the actual therapeutic options for Cannabis sativa L. and the ongoing clinical trials.

scholarly journals Pan-Cancer Analysis of Molecular Characteristics and Oncogenic Role of PRMT5 in Human Cancers

2021 ◽  
Author(s):  
He Liu ◽  
Lexi Huang ◽  
Kunpeng Jia ◽  
Xiaohua Pan
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Molecular Mechanisms ◽  
The Cancer Genome Atlas ◽  
Cancer Development ◽  
Nuclear Antigen ◽  
Molecular Characteristics ◽  
Importance Value ◽  
Pan Cancer

Abstract Background Accumulating evidence supports the correlation of protein arginine methyltransferase 5 (PRMT5) and cancers development. However, the expression and prognostic values of PRMT5 in various cancers have not been clarified. Methods Here, based on The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets, we performed a pan-cancer analysis to explore the expression profile , prognostic value landscape, relationship with tumor-infiltrating immune cells, and potential molecular mechanisms of PRMT5 in cancer development. Moreover, CCK8, wound healing and transwell assays, and western blotting analysis were conducted to evaluate how PRMT5 affects the proliferation and migration, and expression of related hallmarks in breast cancer cells. Results We found that PRMT5 was upregulated in most cancers and PRMT5 harbored distinct prognostic values across different cancer types. In addition, PRMT5 expression was negatively correlated with CD8 + T cells in tumors of cervical squamous cell carcinoma and endocervical adenocarcinoma (CSEC) and Skin Cutaneous Melanoma (SKCM), and positively correlated with the cancer-associated fibroblasts in tumors of adrenocortical carcinoma, CESC, cholangio carcinoma, liver hepatocellular carcinoma, pancreatic adenocarcinoma, and SKCM-Primary. Moreover, the enrichment analysis identified that PRMT5 mechanistically regulated cancers development by acting on DNA and RNA metabolism, and stress response related pathways. By further gene silencing experiment, we confirmed tha t PRMT5 knockdown reduced the proliferative and migrative capacities, as well as the expression of PCNA (proliferating cell nuclear antigen), p21 and HMGB1 (high mobility group box 1 protein) in breast cancer cells. Conclusion Collectively, our pan-cancer study highlighted the importance value of PRMT5 in cancer development and prognosis, and pharmacologic targeting at PRMT5 may provide a novel approach for the treatment of cancers.

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