Role of PFKFB3 and PFKFB4 in Cancer: Genetic Basis, Impact on Disease Development/Progression, and Potential as Therapeutic Targets

PFKFB4 negatively regulated the expression of histone acetyltransferase GCN5 to mediate the tumorigenesis of thyroid cancer

(2020) Huanquan Lu et al.   DEVELOPMENT GROWTH & DIFFERENTIATION

Different transcriptome profiles between human retinoblastoma Y79 cells and an etoposide-resistant subline reveal a chemoresistance mechanism

(2020) Wen-ping Song et al.   BMC Ophthalmology

3PO as a Selective Inhibitor of 6-Phosphofructo-2-Kinase/Fructose-2,6-Biphosphatase 3 in A375 Human Melanoma Cells

(2020) KRZYSZTOF KOTOWSKI et al.   ANTICANCER RESEARCH

A reference map of the human binary protein interactome

(2020) Katja Luck et al.   NATURE

Long noncoding RNA AGPG regulates PFKFB3-mediated tumor glycolytic reprogramming

(2020) Jia Liu et al.   Nature Communications

PFKFB3 inhibitors as potential anticancer agents: Mechanisms of action, current developments, and structure-activity relationships

(2020) Yinhu Wang et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

mTOR Signaling in Cancer and mTOR Inhibitors in Solid Tumor Targeting Therapy

(2019) Tian Tian et al.   INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES

Increased 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase-3 activity in response to EGFR signaling contributes to non-small cell lung cancer cell survival

(2019) Nadiia Lypova et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Inhibition of glucose metabolism through treatment of BRAF mutated metastatic melanoma with vemurafenib.

(2019) Govind Warrier et al.   JOURNAL OF CLINICAL ONCOLOGY

High expression of metabolic enzyme PFKFB4 is associated with poor prognosis of operable breast cancer

(2019) Ling Yao et al.   Cancer Cell International

Role of PFKFB3 and CD163 in Oral Squamous Cell Carcinoma Angiogenesis

(2019) Ji-jia Li et al.   Current Medical Science

PFKFB3 inhibition reprograms malignant pleural mesothelioma to nutrient stress-induced macropinocytosis and ER stress as independent binary adaptive responses

(2019) Sayantani Sarkar Bhattacharya et al.   Cell Death & Disease

The influence of PFK-II overexpression on neuroblastoma patients’ survival may be dependent on the particular isoenzyme expressed, PFKFB3 or PFKFB4

(2019) Sonia E. Trojan et al.   Cancer Cell International

PFKFB3 Inhibition Attenuates Oxaliplatin-Induced Autophagy and Enhances Its Cytotoxicity in Colon Cancer Cells

(2019) Siyuan Yan et al.   INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES

Autophagy inhibition elicits emergence from metastatic dormancy by inducing and stabilizing Pfkfb3 expression

(2019) Alyssa La Belle Flynn et al.   Nature Communications

The role of glycolysis and mitochondrial respiration in the formation and functioning of endothelial tip cells during angiogenesis

(2019) Bahar Yetkin-Arik et al.   Scientific Reports

Autophagy modulates transforming growth factor beta 1 induced epithelial to mesenchymal transition in non-small cell lung cancer cells

(2018) Javad Alizadeh et al.   BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH

The pro-tumorigenic effects of metabolic alterations in glioblastoma including brain tumor initiating cells

(2018) Catherine J. Libby et al.   BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER

RSK Regulates PFK-2 Activity to Promote Metabolic Rewiring in Melanoma

(2018) Thibault Houles et al.   CANCER RESEARCH

The potential utility of PFKFB3 as a therapeutic target

(2018) Ramon Bartrons et al.   EXPERT OPINION ON THERAPEUTIC TARGETS

PFK15, a PFKFB3 antagonist, inhibits autophagy and proliferation in rhabdomyosarcoma cells

(2018) Chunhui Wang et al.   INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE

PFKFB3 is involved in breast cancer proliferation, migration, invasion and angiogenesis

(2018) Fang Peng et al.   INTERNATIONAL JOURNAL OF ONCOLOGY

Expression of PFKFB3 and Ki67 in lung adenocarcinomas and targeting PFKFB3 as a therapeutic strategy

(2018) Xiaoli Li et al.   MOLECULAR AND CELLULAR BIOCHEMISTRY

Inhibiting glycolysis in tumour cells

(2018) Alan Morris   Nature Reviews Endocrinology

SWISS-MODEL: homology modelling of protein structures and complexes

(2018) Andrew Waterhouse et al.   NUCLEIC ACIDS RESEARCH

Targeting PFKFB3 sensitizes chronic myelogenous leukemia cells to tyrosine kinase inhibitor

(2018) Yu Zhu et al.   ONCOGENE

Glioblastoma and chemoresistance to alkylating agents: Involvement of apoptosis, autophagy, and unfolded protein response

(2018) Sabine Hombach-Klonisch et al.   PHARMACOLOGY & THERAPEUTICS

PFKFB3 blockade inhibits hepatocellular carcinoma growth by impairing DNA repair through AKT

(2018) Wen-Kai Shi et al.   Cell Death & Disease

Acetylation accumulates PFKFB3 in cytoplasm to promote glycolysis and protects cells from cisplatin-induced apoptosis

(2018) Fu-Long Li et al.   Nature Communications

An Update on Patents Covering Agents That Interfere with the Cancer Glycolytic Cascade

(2018) Serena Fortunato et al.   ChemMedChem

Therapeutic targeting of PFKFB3 with a novel glycolytic inhibitor PFK158 promotes lipophagy and chemosensitivity in gynecologic cancers

(2018) Susmita Mondal et al.   INTERNATIONAL JOURNAL OF CANCER

Association of single nucleotide autophagy-related protein 5 gene polymorphism rs2245214 with susceptibility to non-small cell lung cancer

(2018) Mohsen Nikseresht et al.   JOURNAL OF CELLULAR BIOCHEMISTRY

Dual-functionality of RASSF1A overexpression in A375 cells is mediated by activation of IL-6/STAT3 regulatory loop

(2018) Mei Yi et al.   MOLECULAR BIOLOGY REPORTS

Metabolic enzyme PFKFB4 activates transcriptional coactivator SRC-3 to drive breast cancer

(2018) Subhamoy Dasgupta et al.   NATURE

Targeting PFKFB3 radiosensitizes cancer cells and suppresses homologous recombination

(2018) Nina M. S. Gustafsson et al.   Nature Communications

Fructose 2,6-Bisphosphate in Cancer Cell Metabolism

(2018) Ramon Bartrons et al.   Frontiers in Oncology

CTLA4 antagonists in phase I and phase II clinical trials, current status  and  future perspectives for cancer therapy

(2018) Bartosz Szostak et al.   EXPERT OPINION ON INVESTIGATIONAL DRUGS

6-Phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 and 4: A pair of valves for fine-tuning of glucose metabolism in human cancer

(2018) Mei Yi et al.   Molecular Metabolism

FOXA1 reprograms the TGF-β-stimulated transcriptional program from a metastasis promoter to a tumor suppressor in nasopharyngeal carcinoma

(2018) Junjun Li et al.   CANCER LETTERS

Metabolic reprogramming ensures cancer cell survival despite oncogenic signaling blockade

(2017) Hui-wen Lue et al.   GENES & DEVELOPMENT

By inhibiting PFKFB3, aspirin overcomes sorafenib resistance in hepatocellular carcinoma

(2017) Sainan Li et al.   INTERNATIONAL JOURNAL OF CANCER

Blockage of glycolysis by targeting PFKFB3 suppresses tumor growth and metastasis in head and neck squamous cell carcinoma

(2017) Hui-Min Li et al.   JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH

The Glycolytic Enzyme PFKFB3 Is Involved in Estrogen-Mediated Angiogenesis via GPER1

(2017) Annalisa Trenti et al.   JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS

Liposomes co-Loaded with 6-Phosphofructo-2-Kinase/Fructose-2, 6-Biphosphatase 3 (PFKFB3) shRNA Plasmid and Docetaxel for the Treatment of non-small Cell Lung Cancer

(2017) Nusrat Chowdhury et al.   PHARMACEUTICAL RESEARCH

Loss of PFKFB4 induces cell death in mitotically arrested ovarian cancer cells

(2017) Charlotte Taylor et al.   Oncotarget

CD44 regulates prostate cancer proliferation, invasion and migration via PDK1 and PFKFB4

(2017) Wei Li et al.   Oncotarget

The molecular basis of targeting PFKFB3 as a therapeutic strategy against cancer

(2017) Luo Lu et al.   Oncotarget

6-Phosphofructo-2-kinase/fructose-2,6-bisphosphatase isoform 3 spatially mediates autophagy through the AMPK signaling pathway

(2017) Siyuan Yan et al.   Oncotarget

PFKFB3 promotes proliferation, migration and angiogenesis in nasopharyngeal carcinoma

(2017) Miao Gu et al.   Journal of Cancer

Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)

(2016) Daniel J Klionsky et al.   Autophagy

Inhibition of 6-phosphofructo-2-kinase (PFKFB3) suppresses glucose metabolism and the growth of HER2+ breast cancer

(2016) Julie O’Neal et al.   BREAST CANCER RESEARCH AND TREATMENT

Inhibition of the Glycolytic Activator PFKFB3 in Endothelium Induces Tumor Vessel Normalization, Impairs Metastasis, and Improves Chemotherapy

(2016) Anna Rita Cantelmo et al.   CANCER CELL

The Emerging Hallmarks of Cancer Metabolism

(2016) Natalya N. Pavlova et al.   Cell Metabolism

UniProt: the universal protein knowledgebase

(2016)   NUCLEIC ACIDS RESEARCH

Targeting of MCT1 and PFKFB3 influences cell proliferation and apoptosis in bladder cancer by altering the tumor microenvironment

(2016) Ke Yao Hu et al.   ONCOLOGY REPORTS

Crystal structure of heart 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFKFB2) and the inhibitory influence of citrate on substrate binding

(2016) Robert B. Crochet et al.   PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS

Photodynamic N-TiO2 Nanoparticle Treatment Induces Controlled ROS-mediated Autophagy and Terminal Differentiation of Leukemia Cells

(2016) Mohammad Amin Moosavi et al.   Scientific Reports

Targeting Metabolic Symbiosis to Overcome Resistance to Anti-angiogenic Therapy

(2016) Laura Pisarsky et al.   Cell Reports

PFK15, a Small Molecule Inhibitor of PFKFB3, Induces Cell Cycle Arrest, Apoptosis and Inhibits Invasion in Gastric Cancer

(2016) Wei Zhu et al.   PLoS One

Overexpression of miR-206 suppresses glycolysis, proliferation and migration in breast cancer cells via PFKFB3 targeting

(2015) Xin Ge et al.   BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS

Novel Therapeutic Targets of Tumor Metabolism

(2015) Rigel J. Kishton et al.   CANCER JOURNAL

MicroRNA-26b inhibits osteosarcoma cell migration and invasion by down-regulating PFKFB3 expression

(2015) W.D. Zheng et al.   GENETICS AND MOLECULAR RESEARCH

Interleukin-6 stimulates aerobic glycolysis by regulating PFKFB3 at early stage of colorectal cancer

(2015) JUN HAN et al.   INTERNATIONAL JOURNAL OF ONCOLOGY

Structure-Based Design of Potent and Selective Inhibitors of the Metabolic Kinase PFKFB3

(2015) Scott Boyd et al.   JOURNAL OF MEDICINAL CHEMISTRY

AMPK and PFKFB3 mediate glycolysis and survival in response to mitophagy during mitotic arrest

(2015) Elena Doménech et al.   NATURE CELL BIOLOGY

Identification of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase as a novel autophagy regulator by high content shRNA screening

(2015) A M Strohecker et al.   ONCOGENE

miR-26b inhibits proliferation, migration, invasion and apoptosis induction via the downregulation of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase-3 driven glycolysis in osteosarcoma cells

(2015) JING-YU DU et al.   ONCOLOGY REPORTS

Steroid Receptor Coactivator-3 (SRC-3/AIB1) as a Novel Therapeutic Target in Triple Negative Breast Cancer and Its Inhibition with a Phospho-Bufalin Prodrug

(2015) Xianzhou Song et al.   PLoS One

Akt inhibition attenuates rasfonin-induced autophagy and apoptosis through the glycolytic pathway in renal cancer cells

(2015) Q Lu et al.   Cell Death & Disease

The expression pattern of PFKFB3 enzyme distinguishes between induced-pluripotent stem cells and cancer stem cells

(2015) Artur Cieślar-Pobuda et al.   Oncotarget

Targeting the sugar metabolism of tumors with a first-in-class 6-phosphofructo-2-kinase (PFKFB4) inhibitor

(2015) Jason Chesney et al.   Oncotarget

A comparative analysis of inhibitors of the glycolysis pathway in breast and ovarian cancer cell line models

(2015) Chrysi Xintaropoulou et al.   Oncotarget

Fructose-2,6-Bisphosphate synthesis by 6-Phosphofructo-2-Kinase/Fructose-2,6-Bisphosphatase 4 (PFKFB4) is required for the glycolytic response to hypoxia and tumor growth

(2015) Jason Chesney et al.   Oncotarget

Endothelial PFKFB3 Plays a Critical Role in Angiogenesis

(2014) Yiming Xu et al.   ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY

The glycolytic enzyme PFKFB3/phosphofructokinase regulates autophagy

(2014) Zhen Yang et al.   Autophagy

MAPK14/p38α-dependent modulation of glucose metabolism affects ROS levels and autophagy during starvation

(2014) Enrico Desideri et al.   Autophagy

Estradiol Stimulates Glucose Metabolism via 6-Phosphofructo-2-kinase (PFKFB3)

(2014) Yoannis Imbert-Fernandez et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

PI3K and cancer: lessons, challenges and opportunities

(2014) David A. Fruman et al.   NATURE REVIEWS DRUG DISCOVERY

Control of Glycolytic Flux by AMP-Activated Protein Kinase in Tumor Cells Adapted to Low pH

(2014) Erin E. Mendoza et al.   Translational Oncology

Mechanisms of regulation of PFKFB expression in pancreatic and gastric cancer cells

(2014) Oleksandr H Minchenko   WORLD JOURNAL OF GASTROENTEROLOGY

Reduced methylation of PFKFB3 in cancer cells shunts glucose towards the pentose phosphate pathway

(2014) Takehiro Yamamoto et al.   Nature Communications

An Overview of Autophagy: Morphology, Mechanism, and Regulation

(2013) Katherine R. Parzych et al.   ANTIOXIDANTS & REDOX SIGNALING

Role of PFKFB3-Driven Glycolysis in Vessel Sprouting

(2013) Katrien De Bock et al.   CELL

Partial and Transient Reduction of Glycolysis by PFKFB3 Blockade Reduces Pathological Angiogenesis

(2013) Sandra Schoors et al.   Cell Metabolism

Regulation of Glycolytic and Mitochondrial Metabolism by Ras

(2013) J. Chesney et al.   CURRENT PHARMACEUTICAL BIOTECHNOLOGY

Increased Concentrations of Fructose 2,6-Bisphosphate Contribute to the Warburg Effect in Phosphatase and Tensin Homolog (PTEN)-deficient Cells

(2013) Lucía Cordero-Espinoza et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Phosphofructokinase deficiency impairs ATP generation, autophagy, and redox balance in rheumatoid arthritis T cells

(2013) Zhen Yang et al.   JOURNAL OF EXPERIMENTAL MEDICINE

Targeting 6-Phosphofructo-2-Kinase (PFKFB3) as a Therapeutic Strategy against Cancer

(2013) B. F. Clem et al.   MOLECULAR CANCER THERAPEUTICS

Functional Metabolic Screen Identifies 6-Phosphofructo-2-Kinase/Fructose-2,6-Biphosphatase 4 as an Important Regulator of Prostate Cancer Cell Survival

(2012) Susana Ros et al.   Cancer Discovery

Progestins activate 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3) in breast cancer cells

(2011) Laura Novellasdemunt et al.   BIOCHEMICAL JOURNAL

LOH on 10p14-p15 targets the PFKFB3 gene locus in human glioblastomas

(2011) Michael Fleischer et al.   GENES CHROMOSOMES & CANCER

Inhibition of Glycolytic Enzymes Mediated by Pharmacologically Activated p53

(2011) Joanna Zawacka-Pankau et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

The JAK2V617F oncogene requires expression of inducible phosphofructokinase/fructose-bisphosphatase 3 for cell growth and increased metabolic activity

(2011) M M Reddy et al.   LEUKEMIA

RNAi screening in glioma stem-like cells identifies PFKFB4 as a key molecule important for cancer cell survival

(2011) V Goidts et al.   ONCOGENE

Block Copolymer Micelles for Controlled Delivery of Glycolytic Enzyme Inhibitors

(2011) Shanjida Akter et al.   PHARMACEUTICAL RESEARCH

Structure-Based Development of Small Molecule PFKFB3 Inhibitors: A Framework for Potential Cancer Therapeutic Agents Targeting the Warburg Effect

(2011) Minsuh Seo et al.   PLoS One

Molecular basis of the fructose-2,6-bisphosphatase reaction of PFKFB3: Transition state and the C-terminal function

(2011) Michael C. Cavalier et al.   PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS

PFKFB4 as a prognostic marker in non-muscle-invasive bladder cancer

(2011) Seok Joong Yun et al.   UROLOGIC ONCOLOGY-SEMINARS AND ORIGINAL INVESTIGATIONS

Fructose 2,6-bisphosphate: the last milestone of the 20th century in metabolic control?

(2010) Mark H. Rider et al.   BIOCHEMICAL JOURNAL

Androgen stimulates glycolysis forde novolipid synthesis by increasing the activities of hexokinase 2 and 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 2 in prostate cancer cells

(2010) Jong-Seok Moon et al.   BIOCHEMICAL JOURNAL

Silencing or Fueling Metastasis with VEGF Inhibitors: Antiangiogenesis Revisited

(2009) Sonja Loges et al.   CANCER CELL

Accelerated Metastasis after Short-Term Treatment with a Potent Inhibitor of Tumor Angiogenesis

(2009) John M.L. Ebos et al.   CANCER CELL

Antiangiogenic Therapy Elicits Malignant Progression of Tumors to Increased Local Invasion and Distant Metastasis

(2009) Marta Pàez-Ribes et al.   CANCER CELL

S100A8/A9 induces autophagy and apoptosis via ROS-mediated cross-talk between mitochondria and lysosomes that involves BNIP3

(2009) Saeid Ghavami et al.   CELL RESEARCH

Abnormalities in Glucose Uptake and Metabolism in Imatinib-Resistant Human BCR-ABL-Positive Cells

(2009) D. J. Kominsky et al.   CLINICAL CANCER RESEARCH

Regulation of glucose metabolism by 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatases in cancer

(2009) Abdullah Yalcin et al.   EXPERIMENTAL AND MOLECULAR PATHOLOGY

Nuclear Targeting of 6-Phosphofructo-2-kinase (PFKFB3) Increases Proliferation via Cyclin-dependent Kinases

(2009) Abdullah Yalcin et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

The PFKFB3 splice variant UBI2K4 is downregulated in high-grade astrocytomas and impedes the growth of U87 glioblastoma cells

(2009) K. Zscharnack et al.   NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY

Small-molecule inhibition of 6-phosphofructo-2-kinase activity suppresses glycolytic flux and tumor growth

(2008) B. Clem et al.   MOLECULAR CANCER THERAPEUTICS

Tumor angiogenesis – A potential target in cancer chemoprevention

(2007) Tariq A. Bhat et al.   FOOD AND CHEMICAL TOXICOLOGY