Nuances of PFKFB3 Signaling in Breast Cancer

Galindo, Claudia; Ganzella, Fernando Augusto de Oliveira; Klassen, Giseli; Ramos, Edneia Amancio de Souza; Acco, Alexandra

doi:10.1016/j.clbc.2022.01.002

Cited by 15 publications

(7 citation statements)

References 86 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…PFKFB3 regulates EC proliferation and vessel sprouting by controlling the formation of filopodia/lamellipodia and directional migration [ 31 , 32 ], which reveals the remarkable significance of the link between metabolism and EC function. PFKFB3 has been linked to the malignancy of tumor cells via enhancing glycolysis in the cytoplasm [ 58 , 59 ] as well as via facilitating DNA repair with its nuclear form [ 60 , 61 ]. Similar to the Warburg effect in tumor cells, healthy ECs produce ATP mainly by aerobic glycolysis [ 31 , 32 ] while in senescent ECs PFKFB3 is significantly downregulated, leading to a decline of glycolysis and glucose tolerance [ 62 ].…”

Section: Discussionmentioning

confidence: 99%

Enhancement of glycolysis-dependent DNA repair regulated by FOXO1 knockdown via PFKFB3 attenuates hyperglycemia-induced endothelial oxidative stress injury

Sun¹,

Chen²,

Li³

et al. 2023

Redox Biology

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 99%

Enhancement of glycolysis-dependent DNA repair regulated by FOXO1 knockdown via PFKFB3 attenuates hyperglycemia-induced endothelial oxidative stress injury

Sun¹,

Chen²,

Li³

et al. 2023

Redox Biology

View full text Add to dashboard Cite

“…PFKFB3 was found to be central element of the mechanism of metabolic switch that regulates the pro-tumor programming of monocytes in human hepatocellular carcinoma ( 48 ). However, in breast and in colorectal cancer, despite large number of studies demonstrating critical role of PFKFB3 in cancer cells metabolism and proliferation, and despite the ongoing studies on the therapeutic targeting of PFKFB3, its role in the programming of immune system on systemic or local levels is largely unexplored ( 49 , 50 ).…”

Section: Discussionmentioning

confidence: 99%

PFKFB3 overexpression in monocytes of patients with colon but not rectal cancer programs pro-tumor macrophages and is indicative for higher risk of tumor relapse

et al. 2023

View full text Add to dashboard Cite

IntroductionCirculating monocytes are main source for tumor-associated macrophages (TAMs) that control tumor growth, angiogenesis, metastasis and therapy resistance. We raised the questions how monocyte programming is affected by growing tumors localized in colon and rectal sections, and how treatment onsets affect monocyte programming in the circulation.MethodsPatients with rectal cancer and colon cancer were enrolled in the study. Peripheral blood monocytes were characterized by phenotypic analysis using flow cytometry, by transcriptomic analysis using RNA sequencing and by gene expression analysis using real-time RT-PCR. Phenotypic analysis was performed with IF/confocal microscopy. Spatial transcriptomic analysis was applied using GeoMX DSP-NGS.ResultsIn patients with rectal cancer, increased amount of CCR2+ monocytes was indicative for the absence of both lymphatic and hematogenous metastasis. In contrast, in patients with colon cancer CD163+ monocytes were indicative for LN metastasis. NGS analysis identified tumor-specific transcriptional programming of monocytes in all CRC patients compared to healthy individuals. The key transcriptional difference between monocytes of patients with colon and rectal cancer was increased expression of PFKFB3, activator of glycolysis that is currently considered as therapy target for major solid cancers. PFKFB3-expressing monocyte-derived macrophages massively infiltrated tumor in colon. Nanostring technology identified correlation of PFKFB3 with amount and tumor-promoting properties of TAMs in colon but not in rectal cancer. PFKFB3 was indicative for tumor relapse specifically in colon cancer.DiscussionOur findings provide essential argument towards CRC definition to cover two clinically distinct cancers – colon cancer and rectal cancer, that differentially interact with innate immunity.

show abstract

“…Studies have shown that the phosphorylation of PFKFB3 is potentially associated with the progression of cancer and angiogenesis (4,(33)(34)(35) and remains a feature of various cancers (36). Hence, we compared the phosphorylation levels of PFKFB3 protein between primary tumor tissues and their normal controls using the CPTAC dataset (Fig.…”

Section: Increased Phosphopfkfb3 Was Detected In Certain Cancersmentioning

confidence: 99%

Systematic pan-cancer analysis identifies 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3) as a biomarker of tumor invasion and metastasis, immunity, and prognosis

Liu

Zhang

et al. 2023

Preprint

View full text Add to dashboard Cite

6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3) is a potent regulator of glycolysis in tumor cells, and high PFKFB3 expression is significantly associated with the invasion and metastasis of several tumors. However, there are no comprehensive reports on whether PFKFB3 promotes tumor invasion and its mechanism in different cancer types. In addition, there are no systematic reports on the effect of PFKFB3 on the stemness and immune infiltration ability of different tumors and on the survival rate of patients. Herein, we conducted a pan-cancer analysis of PFKFB3 with the aim of exploring the key cellular and molecular mechanisms regulating the pathogenesis and progression of human cancers, and propose potential strategies for the prevention and treatment of cancer by targeting PFKFB3. Using bioinformatics analysis and integrative exploration from the Gene Expression Omnibus (GEO) and Cancer Genome Atlas (TCGA) databases, the differential expression of PFKFB3 or phosphorylated PFKFB3 and its correlation with tumor staging and stemness, survival prognosis, and immune invasion were extensively analyzed. The analysis showed differential expression of PFKFB3 in normal tissues and in various cancers. Increased PFKFB3 expression is positively correlated with the invasive ability and immune infiltration of 31 cancers and significantly affects the staging, stemness, prognosis, and survival rate of several cancers. Alterations in phosphorylated PFKFB3 and RNA modifications are also involved in the development and progression of various cancers. PFKFB3 is involved in multiple protein interactions and has complex molecular functions, such as ATP/ADP metabolic and glycolytic processes. Furthermore, PFKFB3 has a high mutation frequency, especially amplification, in multiple tumors. These findings highlight the significance of PFKFB3 in cancer progression, which might serve as a surrogate pan-cancer biomarker to predict the progression and outcome of cancers, as well as the invasion and immune infiltration of different cancers. Ethical compliance: This study did not involve any patient or animal samples and was approved by the academic committee of Tongji University.

show abstract

Nuances of PFKFB3 Signaling in Breast Cancer

Cited by 15 publications

References 86 publications

Enhancement of glycolysis-dependent DNA repair regulated by FOXO1 knockdown via PFKFB3 attenuates hyperglycemia-induced endothelial oxidative stress injury

Enhancement of glycolysis-dependent DNA repair regulated by FOXO1 knockdown via PFKFB3 attenuates hyperglycemia-induced endothelial oxidative stress injury

PFKFB3 overexpression in monocytes of patients with colon but not rectal cancer programs pro-tumor macrophages and is indicative for higher risk of tumor relapse

Systematic pan-cancer analysis identifies 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3) as a biomarker of tumor invasion and metastasis, immunity, and prognosis

Contact Info

Product

Resources

About