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

TitleBlockage of glycolysis by targeting PFKFB3 suppresses tumor growth and metastasis in head and neck squamous cell carcinoma
Authors
KeywordsGlycolysis
HNSCC
Invadopodia
Invasion
Metastasis
PFKFB3
Issue Date2017
Citation
Journal of Experimental and Clinical Cancer Research, 2017, v. 36, n. 1, article no. 7 How to Cite?
AbstractBackground: Many cancers including head and neck squamous cell carcinoma (HNSCC) are characterized by a metabolic rewiring with increased glucose uptake and lactate production, termed as aerobic glycolysis. Targeting aerobic glycolysis presents a promising strategy for cancer therapy. This study investigates the therapeutic potential of glycolysis blockage by targeting phosphofructokinase-2/fructose-2, 6-bisphosphatase 3 (PFKFB3) in HNSCC. Methods: 1-(4-pyridinyl)-3-(2-quinolinyl)-2-propen-1-one (PFK15) was used as a selective antagonist of PFKFB3. Glycolytic flux was determined by measuring glucose uptake, lactate production and ATP yield. PFKFB3 expression was examined using HNSCC tissue arrays. Cell proliferation, apoptosis and motility were analysed. HNSCC xenograft mouse model and metastasis mouse model were established to examine the therapeutic efficacy of PFK15 in vivo. Results: HNSCC showed an increased PFKFB3 expression compared with adjacent mucosal tissues (P < 0.01). Targeting PFKFB3 via PFK15 significantly reduced the glucose uptake, lactate production and ATP generation in HNSCC cell lines. PFK15 suppressed cell proliferation, halted cell cycle progression and induced cell apoptosis. The invadopodia of HNSCC cells was markedly reduced after PFK15 treatment, thereby impairing cell motility and extracellular matrix degradation ability. The in vivo data from the xenograft mice models proved that PFK15 administration suppressed the tumor growth. And the results from the metastatic mice models showed administration of PFK15 alleviated the lung metastasis of HNSCC and extended the life expectancy of mice. Conclusions: The pharmacological inhibition of PFKFB3 via PFK15 suppressed tumor growth and alleviated metastasis in HNSCC, offering a promising strategy for cancer therapy.
Persistent Identifierhttp://hdl.handle.net/10722/345227

 

DC FieldValueLanguage
dc.contributor.authorLi, Hui Min-
dc.contributor.authorYang, Jie Gang-
dc.contributor.authorLiu, Zhuo Jue-
dc.contributor.authorWang, Wei Ming-
dc.contributor.authorYu, Zi Li-
dc.contributor.authorRen, Jian Gang-
dc.contributor.authorChen, Gang-
dc.contributor.authorZhang, Wei-
dc.contributor.authorJia, Jun-
dc.date.accessioned2024-08-15T09:26:01Z-
dc.date.available2024-08-15T09:26:01Z-
dc.date.issued2017-
dc.identifier.citationJournal of Experimental and Clinical Cancer Research, 2017, v. 36, n. 1, article no. 7-
dc.identifier.urihttp://hdl.handle.net/10722/345227-
dc.description.abstractBackground: Many cancers including head and neck squamous cell carcinoma (HNSCC) are characterized by a metabolic rewiring with increased glucose uptake and lactate production, termed as aerobic glycolysis. Targeting aerobic glycolysis presents a promising strategy for cancer therapy. This study investigates the therapeutic potential of glycolysis blockage by targeting phosphofructokinase-2/fructose-2, 6-bisphosphatase 3 (PFKFB3) in HNSCC. Methods: 1-(4-pyridinyl)-3-(2-quinolinyl)-2-propen-1-one (PFK15) was used as a selective antagonist of PFKFB3. Glycolytic flux was determined by measuring glucose uptake, lactate production and ATP yield. PFKFB3 expression was examined using HNSCC tissue arrays. Cell proliferation, apoptosis and motility were analysed. HNSCC xenograft mouse model and metastasis mouse model were established to examine the therapeutic efficacy of PFK15 in vivo. Results: HNSCC showed an increased PFKFB3 expression compared with adjacent mucosal tissues (P < 0.01). Targeting PFKFB3 via PFK15 significantly reduced the glucose uptake, lactate production and ATP generation in HNSCC cell lines. PFK15 suppressed cell proliferation, halted cell cycle progression and induced cell apoptosis. The invadopodia of HNSCC cells was markedly reduced after PFK15 treatment, thereby impairing cell motility and extracellular matrix degradation ability. The in vivo data from the xenograft mice models proved that PFK15 administration suppressed the tumor growth. And the results from the metastatic mice models showed administration of PFK15 alleviated the lung metastasis of HNSCC and extended the life expectancy of mice. Conclusions: The pharmacological inhibition of PFKFB3 via PFK15 suppressed tumor growth and alleviated metastasis in HNSCC, offering a promising strategy for cancer therapy.-
dc.languageeng-
dc.relation.ispartofJournal of Experimental and Clinical Cancer Research-
dc.subjectGlycolysis-
dc.subjectHNSCC-
dc.subjectInvadopodia-
dc.subjectInvasion-
dc.subjectMetastasis-
dc.subjectPFKFB3-
dc.titleBlockage of glycolysis by targeting PFKFB3 suppresses tumor growth and metastasis in head and neck squamous cell carcinoma-
dc.typeArticle-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1186/s13046-016-0481-1-
dc.identifier.pmid28061878-
dc.identifier.scopuseid_2-s2.0-85008622762-
dc.identifier.volume36-
dc.identifier.issue1-
dc.identifier.spagearticle no. 7-
dc.identifier.epagearticle no. 7-
dc.identifier.eissn1756-9966-

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