Phosphofructokinase‐P Modulates P44/42 MAPK Levels in HeLa Cells

Pires, Thyago Rubens Cardim; Albanese, Jamille Mansur; Schwab, Michael; Marette, André; Carvalho, Renato S.; Sola‐Penna, Mauro; Zancan, Patrícia

doi:10.1002/jcb.25774

Cited by 8 publications

(5 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Indeed, the connection between PFKP and the MAPK pathway has been implicated in previous studies. For instance, two independent studies have shown that reduced PFKP expression can attenuate p-ERK1/2 levels in triple-negative breast cancer cell lines and ovarian cancer cell lines [ 47 , 48 ]. Therefore, it is likely that depletion of PFKP disrupts the interaction between PFKP and ERK2, thereby inhibiting the activation of the MAPK/ERK pathway in these cells.…”

Section: Discussionmentioning

confidence: 99%

A positive feedback loop between PFKP and c-Myc drives head and neck squamous cell carcinoma progression

Liu,

Ding,

Tao

et al. 2024

Mol Cancer

View full text Add to dashboard Cite

Background The aberrant expression of phosphofructokinase-platelet (PFKP) plays a crucial role in the development of various human cancers by modifying diverse biological functions. However, the precise molecular mechanisms underlying the role of PFKP in head and neck squamous cell carcinoma (HNSCC) are not fully elucidated. Methods We assessed the expression levels of PFKP and c-Myc in tumor and adjacent normal tissues from 120 HNSCC patients. A series of in vitro and in vivo experiments were performed to explore the impact of the feedback loop between PFKP and c-Myc on HNSCC progression. Additionally, we explored the therapeutic effects of targeting PFKP and c-Myc in HNSCC using Patient-Derived Organoids (PDO), Cell Line-Derived Xenografts, and Patients-Derived Xenografts. Results Our findings indicated that PFKP is frequently upregulated in HNSCC tissues and cell lines, correlating with poor prognosis. Our in vitro and in vivo experiments demonstrate that elevated PFKP facilitates cell proliferation, angiogenesis, and metastasis in HNSCC. Mechanistically, PFKP increases the ERK-mediated stability of c-Myc, thereby driving progression of HNSCC. Moreover, c-Myc stimulates PFKP expression at the transcriptional level, thus forming a positive feedback loop between PFKP and c-Myc. Additionally, our multiple models demonstrate that co-targeting PFKP and c-Myc triggers synergistic anti-tumor effects in HNSCC. Conclusion Our study demonstrates the critical role of the PFKP/c-Myc positive feedback loop in driving HNSCC progression and suggests that simultaneously targeting PFKP and c-Myc may be a novel and effective therapeutic strategy for HNSCC.

show abstract

Section: Discussionmentioning

confidence: 99%

A positive feedback loop between PFKP and c-Myc drives head and neck squamous cell carcinoma progression

Liu,

Ding,

Tao

et al. 2024

Mol Cancer

View full text Add to dashboard Cite

show abstract

“…Although there are no reports on PFKP in CC, this enzyme has been found to be overexpressed in HeLa cells 39 and related to the activation of tumor survival pathways via P44/42 mitogen-activated protein kinase (MAPK). 40 Increased PFKP expression and activity are related to neoplastic activity, metastasis, and decreased survival in several types of cancer, primarily brain, kidney, and breast cancers. 41,42 Other studies have shown that the inhibition of PFKP with specific siRNAs in lung cancer cell lines 37 and murine tumor models of leukemia 43 decreased the expression of the enzyme, the glycolysis rate, and glucose, lactic acid, and ATP concentrations in the supernatant of cell cultures; tumor growth, and progression was also observed.…”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

The mRNA and protein levels of the glycolytic enzymes lactate dehydrogenase A (LDHA) and phosphofructokinase platelet (PFKP) are good predictors of survival time, recurrence, and risk of death in cervical cancer patients

et al. 2023

View full text Add to dashboard Cite

IntroductionPatients with cervical cancer (CC) may experience local recurrence very often after treatment; when only clinical parameters are used, most cases are diagnosed in late stages, which decreases the chance of recovery. Molecular markers can improve the prediction of clinical outcome. Glycolysis is altered in 70% of CCs, so molecular markers of this pathway associated with the aggressiveness of CC can be identified.MethodsThe expression of 14 glycolytic genes was analyzed in 97 CC and 29 healthy cervical tissue (HCT) with microarray; only LDHA and PFKP were validated at the mRNA and protein levels in 36 of those CC samples and in 109 new CC samples, and 31 HCT samples by qRT–PCR, Western blotting, or immunohistochemistry. A replica analysis was performed on 295 CC from The Cancer Genome Atlas (TCGA) database.ResultsThe protein expression of LDHA and PFKP was associated with poor overall survival [OS: LDHA HR = 4.0 (95% CI = 1.4–11.1); p = 8.0 × 10−3; PFKP HR = 3.3 (95% CI = 1.1–10.5); p = 4.0 × 10−2] and disease‐free survival [DFS: LDHA HR = 4.5 (95% CI = 1.9–10.8); p = 1.0 × 10−3; PFKP HR = 3.2 (95% CI = 1.2–8.2); p = 1.8 × 10−2] independent of FIGO clinical stage, and the results for mRNA expression were similar. The risk of death was greater in patients with overexpression of both biomarkers than in patients with advanced FIGO stage [HR = 8.1 (95% CI = 2.6–26.1; p = 4.3 × 10−4) versus HR = 7 (95% CI 1.6–31.1, p = 1.0 × 10−2)] and increased exponentially as the expression of LDHA and PFKP increased.ConclusionsLDHA and PFKP overexpression at the mRNA and protein levels was associated with poor OS and DFS and increased risk of death in CC patients regardless of FIGO stage. The measurement of these two markers could be very useful for evaluating clinical evolution and the risk of death from CC and could facilitate better treatment decision making.

show abstract

“…Although there are no PFKP reports in CC, this enzyme has been found to be overexpressed in HeLa cells [35] and related to the activation of tumor survival pathways via P44/42 mitogen-activated protein kinase (MAPK) [36]. Increased PFKP expression and activity are related to neoplastic activity, metastasis production, and decreased survival in several types of cancer, primarily brain, kidney, and breast cancers [37], [38].…”

Section: Discussionmentioning

confidence: 99%

Gene expression levels of the glycolytic enzymes lactate dehydrogenase A (LDHA) and phosphofructokinase platelet (PFKP) are good predictors of survival time, recurrence and risk of death in cervical cancer

Bolaños

Alfaro

Espinosa

et al. 2022

Preprint

View full text Add to dashboard Cite

Background. Up to 74% of patients with cervical cancer (CC) may experience recurrence after their treatment, and most of them are identified late when only the clinical parameters are used, which decreases their chances of recovery. Molecular markers can improve the prediction of clinical outcome and identify therapeutic targets in CC. Glycolysis is altered in 70% of CCs, so it could be a metabolic pathway in which molecular markers associated with the aggressiveness of CC can be identified. Methods. The expression of 14 glycolytic genes was analyzed in 118 CC samples by microarrays, and only LDHA and PFKP were validated by qRT PCR (n=58) and in second and third replicates by Western blotting (n=69) and immunohistochemistry (n=18). Results. LDHA and PFKP were associated with poor overall survival [OS: LDHA HR=3.0 (95% CI= 1.1 to 8.2); p=2.9 x 10-2; PFKP HR=3.4 (95% CI= 1.1 to 10.5); p= 3.5 x 10-2] and disease-free survival [DFS: LDHA HR=2.7 (95% CI= 1.6 to 6.3); p=2.6 x 10-2] independent of FIGO clinical stage. The risk of death was greater when both biomarkers were overexpressed than when using only FIGO stage [HR =7 (95% CI 1.6 to 31.1, p=1.0 x 10-2) versus HR=8.1 (95% CI=2.6 to 26.1; p=4.3 x 10-4)] and increased exponentially as the expression of LDHA and PFKP increased. Conclusions. LDHA and PFKP at the mRNA and protein levels were associated with poor overall survival, disease-free survival and increased risk of death of patients with CC regardless of FIGO stage. The measurement of expression of these two markers could be very useful to evaluate the clinical evolution and the risk of death from CC and to make better therapeutic decisions at the beginning of treatment.

show abstract

Phosphofructokinase‐P Modulates P44/42 MAPK Levels in HeLa Cells

Cited by 8 publications

References 47 publications

A positive feedback loop between PFKP and c-Myc drives head and neck squamous cell carcinoma progression

A positive feedback loop between PFKP and c-Myc drives head and neck squamous cell carcinoma progression

The mRNA and protein levels of the glycolytic enzymes lactate dehydrogenase A (LDHA) and phosphofructokinase platelet (PFKP) are good predictors of survival time, recurrence, and risk of death in cervical cancer patients

Gene expression levels of the glycolytic enzymes lactate dehydrogenase A (LDHA) and phosphofructokinase platelet (PFKP) are good predictors of survival time, recurrence and risk of death in cervical cancer

Contact Info

Product

Resources

About