• cancer
• markers
• stem cells
• treatment

• Neoplastic Stem Cells/metabolism
• Neoplastic Stem Cells/pathology
• Humans
• Animals
• Neoplasms/metabolism
• Neoplasms/pathology
• Neoplasms/therapy
• Glycolysis
• Oxidative Phosphorylation
• Tumor Microenvironment
• Mitochondria/metabolism

• AMP‐activated protein kinase
• PGC‐1α
• PPARGC1A
• glioblastoma
• hypoxia
• metabolic plasticity
• tumour microenvironment

• Glioblastoma/metabolism
• Glioblastoma/genetics
• Glioblastoma/pathology
• Humans
• Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/metabolism
• Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/genetics
• AMP-Activated Protein Kinases/metabolism
• AMP-Activated Protein Kinases/genetics
• Brain Neoplasms/metabolism
• Brain Neoplasms/genetics
• Brain Neoplasms/pathology
• Cell Line, Tumor

• 70114005 Deutsche Krebsforschungsstiftung
• Frankfurter Forschungs Förderung
• DFG 2175/1-1 Deutsche Forschungsgemeinschaft
• FuGGProject-ID403765277 Deutsche Forschungsgemeinschaft
• Deutsche Forschungsgemeinschaft

• SYF formula
• breast cancer
• invasion and metastasis
• molecular docking
• network pharmacology

• Triple Negative Breast Neoplasms/drug therapy
• Triple Negative Breast Neoplasms/pathology
• Triple Negative Breast Neoplasms/metabolism
• Triple Negative Breast Neoplasms/genetics
• Drugs, Chinese Herbal/pharmacology
• Drugs, Chinese Herbal/therapeutic use
• Drugs, Chinese Herbal/chemistry
• Humans
• Animals
• Female
• Mice
• Cell Line, Tumor
• Cell Proliferation/drug effects
• Molecular Docking Simulation
• Xenograft Model Antitumor Assays
• Network Pharmacology
• Cell Movement/drug effects
• Mice, Nude
• Luteolin/pharmacology
• Luteolin/therapeutic use
• Mice, Inbred BALB C
• Quercetin/pharmacology
• Quercetin/chemistry
• Medicine, Chinese Traditional
• Gene Expression Regulation, Neoplastic/drug effects

• Apoptosis
• Cisplatin
• PPARγ
• Pioglitazone
• Triple-negative breast cancer

• Epithelial to mesenchymal transition
• Mammary cancer
• Multi-generational epigenetic effects
• Peroxisome proliferator-activated receptor gamma
• Polycyclic aromatic hydrocarbons
• Prenatal exposure

• Animals
• Female
• Humans
• Mice
• Pregnancy
• Biomarkers
• Body Weight
• Breast Neoplasms/chemically induced
• Epithelial-Mesenchymal Transition
• Polycyclic Aromatic Hydrocarbons/metabolism
• Polycyclic Aromatic Hydrocarbons/toxicity
• PPAR gamma/genetics
• PPAR gamma/metabolism

• U01 ES026122 NIEHS NIH HHS

• W81XWH-20-1-0029 United States Department of Defense | United States Army | Army Medical Command | Congressionally Directed Medical Research Programs (CDMRP)

• Cancer stem cells
• Cellular plasticity
• EMT
• Metabolism
• Signaling pathways
• Solid tumors
• Tumor microenvironment

• Humans
• Tumor Microenvironment
• Neoplasms/pathology
• Neoplastic Stem Cells/metabolism
• Epithelial-Mesenchymal Transition

• Tabriz University of Medical Sciences

• 202210344008 National College Students Innovation and Entrepreneurship Training Program
• 2021-QNRC2-B13 Young Elite Scientists Sponsorship Program by CACM
• 2022E10021 Key Laboratory of Prevention, Diagnosis and Therapy of Upper Gastrointestinal Cancer of Zhejiang Province

• cervical cancer
• lipid metabolism
• radiation
• p53
• pparγ and cd36

• Cancer Stem Cell
• Metaboloepigenetics
• Metabostemness
• Mitophagy
• Oncometabolism

• cancer stem cell
• fatty acid metabolism
• glutamninolysis
• glycolysis
• metabolic pathway
• metabolic plasticity
• mitochondrial respiration

• Animals
• Glutamine/metabolism
• Humans
• Metabolic Networks and Pathways
• Mitochondria/metabolism
• Molecular Targeted Therapy
• Neoplastic Stem Cells/metabolism
• Oxidative Phosphorylation

• MOST104-2314-B-715-003-MY3, MOST104-2627-M-715-002, MOST104-2320-B-715-006-MY2, MOST105-2627-M-715-001, MOST106-2627-M-371-001, MOST106-2320-B-371-002, MOST107-2320-B-371-002, MOST108-2320-B-371-001 and MOST 109-2320-B-371-004, MOST 109-2314-B-038-021-MY3 Ministry of Science and Technology, Taiwan
• 107-CCH-NPI-052 and108-CCH-MST-168 Changhua Christian Hospital

• EMT
• ID1
• PGC1α
• TCF4
• TWIST1
• lung cancer
• metastasis

Breast cancer commonly affects women of older age; however, in developing countries, up to 20% of breast cancer cases present in young women (younger than 40 years as defined by oncology literature). Breast cancer in young women is often defined to be aggressive in nature, usually of high histological grade at the time of diagnosis and negative for endocrine receptors with poor overall survival rate. Several researchers have attributed this aggressive nature to a hidden unique biology. However, findings in this aspect remain controversial. Thus, in this article, we aimed to review published work addressing somatic mutations, chromosome copy number variants, single nucleotide polymorphisms, differential gene expression, microRNAs and gene methylation profile of early-onset breast cancer, as well as its altered pathways resulting from those aberrations. Distinct biology behind early-onset of breast cancer was clear among estrogen receptor-positive and sporadic cases. However, further research is needed to determine and validate specific novel markers, which may help in customizing therapy for this group of patients.

• breast cancer in young age
• copy number variants
• differential gene expression
• early-onset breast cancer
• extracellular matrix protein-coding genes
• gene methylation
• somatic mutations

• Breast cancer metastasis
• EMT
• TGFβ
• miRNAs

• PPARG2 Pro12Ala polymorphism
• cancer
• diet
• diet-gene interactions
• nutrients
• peroxisome proliferator-activated receptor-γ2

Metabolic reprogramming of cancer is now considered a hallmark of many malignant tumors, including breast cancer, which remains the most commonly diagnosed cancer in women all over the world. One of the main challenges for the effective treatment of breast cancer emanates from the existence of a subpopulation of tumor-initiating cells, known as cancer stem cells (CSCs). Over the years, several pathways involved in the regulation of CSCs have been identified and characterized. Recent research has also shown that CSCs are capable of adopting a metabolic flexibility to survive under various stressors, contributing to chemo-resistance, metastasis, and disease relapse. This review summarizes the links between the metabolic adaptations of breast cancer cells and CSC-associated pathways. Identification of the drivers capable of the metabolic rewiring in breast cancer cells and CSCs and the signaling pathways contributing to metabolic flexibility may lead to the development of effective therapeutic strategies. This review also covers the role of these metabolic adaptation in conferring drug resistance and metastasis in breast CSCs.

• breast cancer
• cancer stem cells
• metabolism
• signaling pathways

Mitochondria as the cellular energy powerhouses provide a common site for multiple metabolic reactions in order to cover energy and biomolecule demands, thus integrating the diverse metabolic pathways to endow cells with metabolic adaptation. Mitochondrial plasticity is normally regulated by mitochondrial dynamics, mitochondrial metabolism and mitochondrial biogenesis. Given that tumor cells and T cells share the metabolic similarities of survival, proliferation, expansion as well as effector function, manipulation of mitochondrial plasticity would change the metabolic competition between “foe” and “friend” during tumor malignant progression. On the one hand, for “foe” tumor cells, mitochondrial plasticity provides the enhancement of tumor metastasis and the development of resistance to‘ diverse antitumor drugs. On the other hand, for “friend” T cells, mitochondrial plasticity promotes the generation of long-term memory T (T_M) cells and alleviates the exhaustion of tumor-infiltrating lymphocytes (TILs). Therefore, downregulation of mitochondrial plasticity of tumor cells through engineering tumor-targeting nanoparticles may effectively potentiate metabolic vulnerability and re-sensitize tumor to relevant therapeutic treatment. On the contrary, upregulation of mitochondrial plasticity of T cells through optimizing adoptive cellular immunotherapy (ACI) or chimeric antigen receptor (CAR)-T cell therapy would provide T cells with the robust metabolic fitness and the persistent immune function, thus blocking tumor metastasis and reoccurrence.

• T cells exhaustion
• memory T cells
• mitochondrial plasticity
• therapeutic resistance
• tumor metastasis

One of the most serious cancers among women is breast cancer. This disease is the first reason for the death of women due to cancer. Increasing breast cancer risk may associate with many factors including genetic, reproductive factors, people's lifestyle, metabolic syndrome (MS) and hormones. MS has been known as a risk factor for prostate, pancreatic, breast and colorectal cancers. The purpose of this review is to identify the relationship between MS components and breast cancer individually. This study was performed by researching electronic database references including PubMed, Google Scholar, CINAHL ProQuest, and web of science through 2019. The effect of MS with its components and breast cancer was reported in many studies. Nevertheless, a thorough understanding of the mechanisms involved remains a challenge. However, one can take several preventive measures, including a proper diet, which is one of the most important determinants of metabolic status. Also, general preventive recommendations are including reducing alcohol consumption, red meat and total fat in the diet. Moreover, increasing the consumption of vegetable and fruit reduce the proportion of MS patients to improve the outcome of breast cancer patients.

• Breast cancer
• electronic database
• metabolic syndrome
• natural products

• Cancer
• Metabolism
• Metastasis
• PGC-1α
• Tumor

• aging
• autophagy
• heart
• mitochondria
• telomerase

• diabetic nephropathy
• epithelial-to-mesenchymal transition
• peroxisome proliferator-activated receptors γ
• phosphatase and tensin homolog deleted on chromosome 10
• renal tubulointerstitial fibrosis

• Breast cancer
• CDK2AP1
• breast cancer specimen
• human breast cancer
• tumour suppressor role
• tumour-suppressive function

• Augmenter of liver regeneration
• Ischemia–reperfusion injury
• Mitochondrial biogenesis
• Reactive oxygen species

• Adenosine Triphosphate/metabolism
• Apoptosis
• Cell Line, Transformed
• Cytochrome Reductases/antagonists & inhibitors
• Cytochrome Reductases/genetics
• Cytochrome Reductases/metabolism
• DNA, Mitochondrial/metabolism
• Gene Expression Regulation
• Gene Silencing
• Humans
• Kidney/pathology
• Kidney Tubules, Proximal/metabolism
• Kidney Tubules, Proximal/pathology
• Mitochondria/genetics
• Mitochondria/metabolism
• Mitochondria/pathology
• Organelle Biogenesis
• Oxidative Stress
• Oxidoreductases Acting on Sulfur Group Donors
• Reactive Oxygen Species/metabolism
• Reperfusion Injury/metabolism
• Reperfusion Injury/pathology

• cancer stem cells
• metabolism
• mitochondria

Metabolic reprogramming confers cancer cells the ability to grow and survive under nutrient-depleted or stressful microenvironments. The amplification of oncogenes, the loss of tumor suppressors, as well as context- and lineage-specific determinants can converge and profoundly affect the metabolic status of cancer cells. Cumulating evidences suggest that highly glycolytic cells under the influence of oncogenes such as BRAF, or evolving in hypoxic microenvironments, will promote metastasis through modulation of multiple steps of tumorigenesis such as the epithelial-to-mesenchymal transition (EMT). On the contrary, increased reliance on mitochondrial respiration is associated with hyperplasic rather than metastatic disease. The PGC-1α transcriptional coactivator, a master regulator of mitochondrial biogenesis, has recently been shown to exert antimetastatic effects in cancer, notably through inhibition of EMT. Besides, PGC-1α has the opposite role in specific cancer subtypes, in which it appears to provide growth advantages. Thus, the regulation and role of PGC-1α in cancer is not univocal, and its use as a prognostic marker appears limited given its highly dynamic nature and its multifaceted regulation by transcriptional and posttranslational mechanisms. Herein, we expose key oncogenic and lineage-specific modules that finely regulate PGC-1α to promote or dampen the metastatic process. We propose a unifying model based on the systematic analysis of its controversial implication in cancer from cell proliferation to EMT and metastasis. This short review will provide a good understanding of current challenges associated with the study of PGC-1α.

• OXPHOS
• PGC-1
• cancer
• metastasis
• microenvironment
• oncogenes
• reactive oxygen species
• tumor suppressors

Cellular adaptive mechanisms are crucial for tumorigenesis and a common feature in solid tumor progression. Hypoxia-inducible factor-1α (HIF-1α) facilitates the biological response to hypoxia, advancing angiogenesis and metastatic potential of the tumor. The peroxisome proliferator–activated receptor γ coactivators 1α (PGC-1α) enhances mitochondrial biogenesis, favored by migratory/invasive cancer cells. We conducted a prospective, long-term follow up study to determine whether HIF-1α and PGC-1α can be implemented as predictive biomarker in breast cancer. HIF-1α and PGC-1α plasma concentrations were measured in patients and in healthy controls by enzyme linked immune sorbent assay. Breast cancer patients had significantly higher HIF-1α and PGC-1α levels, which correlated with clinicopathological features, overall with more aggressive cancer characteristics. Disease free and overall survival of breast cancer patients with high HIF-1α and PGC-1α were significantly poorer than in patients with low plasma levels. In multivariate analysis, high amount of PGC-1α showed independent prognostic value. Our data suggests that HIF-1α and PGC-1α may be promising, noninvasive, biomarkers with a high potential for future clinical implication to identify subgroups of patients with poorer prognosis and to indicate early, subclinical metastasis.

• ELISA
• HIF-1α
• PGC-1α
• breast cancer
• prognosis

The PGC1 family (Peroxisome proliferator-activated receptor γ (PPARγ) coactivators) of transcriptional coactivators are considered master regulators of mitochondrial biogenesis and function. The PGC1α isoform is expressed especially in metabolically active tissues, such as the liver, kidneys and brain, and responds to energy-demanding situations. Given the altered and highly adaptable metabolism of tumor cells, it is of interest to investigate PGC1α in cancer. Both high and low levels of PGC1α expression have been reported to be associated with cancer and worse prognosis, and PGC1α has been attributed with oncogenic as well as tumor suppressive features. Early in carcinogenesis PGC1α may be downregulated due to a protective anticancer role, and low levels likely reflect a glycolytic phenotype. We suggest mechanisms of PGC1α downregulation and how these might be connected to the increased cancer risk that obesity is now known to entail. Later in tumor progression PGC1α is often upregulated and is reported to contribute to increased lipid and fatty acid metabolism and/or a tumor cell phenotype with an overall metabolic plasticity that likely supports drug resistance as well as metastasis. We conclude that in cancer PGC1α is neither friend nor foe, but rather the obedient servant reacting to metabolic and environmental cues to benefit the tumor cell.

• PGC1α
• PPARGC1A
• tumor cell metabolism
• tumor progression

• Colorectal cancer
• Lymph node metastasis
• PGC-1α
• Prognosis

Aconitine, a diterpenoid alkaloids derived from Aconitum plants, is widely employed to treat various diseases. The aim of the present study was to investigate the apoptotic effect of aconitine in H9c2 cardiac cells. H9c2 cell apoptosis induced by aconitine was detected by a Cell Counting kit-8 assay, DAPI staining, Annexin V-FITC/propidium iodide double staining and western blotting. The effects of aconitine on reactive oxygen species levels and mitochondrial membrane potential were confirmed by fluorescence microscopy and flow cytometry. In addition, ATP contents were determined using a ATP-dependent bioluminescence assay kit. The levels of peroxisome proliferator activated receptor γ co-activator 1α (PGC-1α) expression and apoptosis-associated proteins including Caspase-3, B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax) and Cytochrome c were also assessed. Taken together, the results indicated that aconitine may inhibit cell viability, decrease PGC-1α expression, induce mitochondrial dysfunctions, upregulate Cytochrome c, Bax and Caspase-3, and downregulate Bcl-2, suggesting that aconitine may induce apoptosis through mitochondria-mediated signaling pathways in H9c2 cells.

• Breast Neoplasms/genetics
• Breast Neoplasms/pathology
• Female
• Genetic Predisposition to Disease
• Genome-Wide Association Study
• Gonadal Steroid Hormones/genetics
• Humans
• Polymorphism, Single Nucleotide
• Purines/metabolism
• Receptors, Calcitriol/genetics
• Risk Factors
• Signal Transduction/genetics

• R01 HG005084 NHGRI NIH HHS
• R37 CA070867 NCI NIH HHS
• R01 CA064277 NCI NIH HHS
• R01 CA063464 NCI NIH HHS
• R01 CA132839 NCI NIH HHS
• U01 CA098758 NCI NIH HHS
• R01 CA192178 NCI NIH HHS
• R37 CA054281 NCI NIH HHS
• U01 CA098710 NCI NIH HHS
• R01 HG005853 NHGRI NIH HHS
• R01 CA159712 NCI NIH HHS
• U01 CA098216 NCI NIH HHS
• U01 HG005922 NHGRI NIH HHS
• U01 CA098233 NCI NIH HHS
• R01 CA054281 NCI NIH HHS
• U01 CA063464 NCI NIH HHS
• Division of Biological Infrastructure
• National Institutes of Health
• Canadian Institute for Advanced Research

• Cancer
• Mitochondria
• Nitric oxide
• Nitric oxide synthase
• Respiratory chain

• Animals
• Cell Transformation, Neoplastic
• Electron Transport
• Humans
• Mitochondria/metabolism
• Mitochondrial Diseases/metabolism
• Neoplasm Proteins/metabolism
• Neoplasms/metabolism
• Nitric Oxide/metabolism
• Nitric Oxide Synthase/metabolism
• Organelle Biogenesis
• Tumor Microenvironment

• R01 AG036871 NIA NIH HHS
• R01 EY010804 NEI NIH HHS
• R01 NS079965 NINDS NIH HHS
• R21 ES025673 NIEHS NIH HHS

Ischemia/reperfusion injury triggers acute kidney injury (AKI) by aggravating oxidative stress mediated mitochondria dysfunction. The peroxisome proliferator-activated receptor gamma coactivator 1α (PGC-1α) is a master player that regulates mitochondrial biogenesis and the antioxidant response. We postulated that PGC-1α functions as cytoprotective effector in renal cells and that its regulation mechanism is coordinated by nuclear factor erythroid 2-related factor 2 (Nrf-2). In this study, to understand the effect and molecular mechanisms of PGC-1α, we developed an empty vector or PGC-1α-overexpressing stable cell lines in HK-2 cells (Mock or PGC-1α stable cells). PGC-1α overexpression increased the viability of cells affected by H₂O₂ mediated injury, protected against H₂O₂-mediated apoptotic events and inhibited reactive oxygen species accumulation in the cytosol and mitochondria as compared to that in Mock cells. The cytoprotective effect of PGC-1α was related to Nrf-2 upregulation, which was counteracted by Nrf-2-specific knockdown. Using inhibitor of p38, we found that regulation of the p38/glycogen synthase kinase 3β (GSK3β)/Nrf-2 axis was involved in the protective effects of PGC-1α. Taken together, we suggest that PGC-1α protects human renal tubule cells from H₂O₂-mediated apoptotic injury by upregulating Nrf-2 via GSK3β inactivation mediated by activated p38.

Peroxisome proliferator-activated receptor γ coactivator 1α (PGC1α) is a key modulator of mitochondrial biogenesis. It is a coactivator of multiple transcription factors and regulates metabolic processes. However, little is known about the expression and function of PGC1α in glioblastoma multiforme (GBM), the most prevalent and invasive type of brain tumor. The purpose of the present study was to investigate the biological function, localization and expression of PGC1α in GBM. It was observed that PGC1α expression is increased in the tumor cells, and a higher level of expression was observed in the mitochondria. Bioinformatics analyses identified that metabolic and mitochondrial genes were highly expressed in GBM cells, with a high PGC1α mRNA expression. Notably, mitochondrial function-associated genes were highly expressed in cells alongside high PGC1α expression. Collectively, the results of the present study indicate that PGC1α is associated with mitochondrial dysfunction in GBM and may have a role in tumor pathogenesis and progression.

• bioinformatics
• coactivator 1α
• glioblastoma multiforme
• mitochondria
• peroxisome proliferator- activated receptor γ

Psoriasin, which is also known as S100A7, is a member of the S100 protein family, a group of calcium-responsive signalling proteins. Psoriasin expression remains high in patients with psoriasis, whereas it is downregulated in patients with invasive breast carcinoma. This observation suggests that this protein may be a notable marker of keratinocyte function and differentiation during wound healing. The aim of the present study was to determine the cellular impact of Psoriasin in keratinocytes, which are the primary cell type associated with wound healing. Psoriasin expression in wound tissues was examined using reverse transcription-quantitative polymerase chain reaction and immunochemical staining. Knockdown of Psoriasin in HaCaT cells was performed using anti-Psoriasin ribozyme transgenes and the effect on growth, adhesion and migration of keratinocytes was subsequently determined using in vitro cellular functional assays. Psoriasin expression is upregulated in wounds, particularly at the wound edges. The present study demonstrated that Psoriasin is expressed in keratinocytes and is a fundamental regulator of keratinocyte migration. Significant increases in the rate of keratinocyte adhesion, migration and growth were observed in Psoriasin-deficient cells (P<0.01 vs. control). Application of small inhibitors identified the potential association of neural Wiskott-Aldrich syndrome protein, focal adhesion primase and rho-associated protein kinase signalling pathways with Psoriasin-regulated cell adhesion and motility. In conclusion, Psoriasin serves an important role in the wound healing process, suggesting that it may be utilized as a potential wound healing biomarker.

• Psoriasin
• adhesion and proliferation
• migration
• wound healing

• metabolism
• stress response
• transcription

Thiazolidinediones (TZDs) are synthetic ligands of Peroxisome-Proliferator-Activated Receptor gamma (PPARγ). Troglitazone, rosiglitazone, and pioglitazone have been approved for treatment of diabetes mellitus type II. All three compounds, together with the first TZD ciglitazone, also showed an antitumor effect in preclinical studies and a beneficial effect in some clinical trials. This review summarizes hypotheses on the role of PPARγ in tumors, on cellular targets of TZDs, antitumor effects of monotherapy and of TZDs in combination with other compounds, with a focus on their role in the treatment of differentiated thyroid carcinoma. The results of chemopreventive effects of TZDs are also considered. Existing data suggest that the action of TZDs is highly complex and that actions do not correlate with cellular PPARγ expression status. Effects are cell-, species-, and compound-specific and concentration-dependent. Data from human trials suggest the efficacy of TZDs as monotherapy in prostate cancer and glioma and as chemopreventive agent in colon, lung, and breast cancer. TZDs in combination with other therapies might increase antitumor effects in thyroid cancer, soft tissue sarcoma, and melanoma.

• Animals
• Carcinogenesis/genetics
• Cell Line, Tumor
• Cell Proliferation/genetics
• Colorectal Neoplasms/genetics
• Colorectal Neoplasms/pathology
• Diazepam Binding Inhibitor/genetics
• Gene Expression Regulation, Neoplastic
• Gene Knockdown Techniques
• HEK293 Cells
• HT29 Cells
• Humans
• Mice
• Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
• Sp1 Transcription Factor/genetics
• Transcription Factors/antagonists & inhibitors
• Transcription Factors/genetics
• Transfection
• Up-Regulation/genetics

• Aged
• Aged, 80 and over
• Breast Neoplasms/genetics
• Breast Neoplasms/metabolism
• Breast Neoplasms/pathology
• Female
• Gene Expression
• Gene Expression Profiling
• Gene Expression Regulation, Neoplastic
• Humans
• Immunohistochemistry
• Middle Aged
• Neoplasm Grading
• Receptor, ErbB-2/metabolism
• Receptors, Cytoplasmic and Nuclear/genetics
• Receptors, Cytoplasmic and Nuclear/metabolism
• Receptors, Estrogen/metabolism
• Receptors, Progesterone/metabolism
• Risk Factors
• Stromal Cells/metabolism