Increased expression of PFKFB3 in oral squamous cell carcinoma and its association with lymphangiogenesis

Li, Jiajia; Tang, Xiaodi

doi:10.1016/j.oooo.2021.02.005

Cited by 4 publications

(3 citation statements)

References 36 publications

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“…PFKFB3 -modulating glycolysis is essential for lymphotoxin α–promoted tumor angiogenesis in HNSCC [ 51 ]. Many studies have indicated that PFKFB3 is involved in the angiogenesis of OSCC [ 52 ], especially for lymphangiogenesis [ 53 ]. Our results suggest that oral cancer patients with higher PFKFB3 expression exhibits lymph node metastasis (Table 4 ), implying that PFKFB3 might promote lymphangiogenesis for lymph node metastasis.…”

Section: Discussionmentioning

confidence: 99%

Comparative clinical significance and biological roles of PFKFB family members in oral squamous cell carcinoma

Hu,

Shu,

Lee

et al. 2023

Cancer Cell Int

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Background Cancer cells promote glycolysis, which supports rapid cell growth and proliferation. Phosphofructokinase-fructose bisphosphatases (PFKFBs), a family of bidirectional glycolytic enzymes, play key roles in the regulation of glycolysis in many types of cancer. However, their roles in oral squamous cell carcinoma (OSCC), the most common type of oral cancer, are still unknown. Methods We compared the gene expression levels of PFKFB family members and analyzed their clinical significance in oral cancer patients, whose clinical data were obtained the Cancer Genome Atlas database. Moreover, real-time quantitative polymerase chain reaction, western blotting, assays for cell viability, cell cycle, cell migration and viability of cell spheroid were performed in scramble and PFKFB-silenced cells. Results We discovered that PFKFB3 expression in tumor tissues was slightly higher than that in tumor adjacent normal tissues but that PFKFB4 expression was significantly higher in the tumor tissues of oral cancer patients. High PFKFB3 and PFKFB4 expression had different effects on the prognosis of oral cancer patients with different clinicopathological outcomes. Our data showed that PFKFB3 and PFKFB4 play different roles; PFKFB3 is involved in cell viability, G2/M cell cycle progression, invasion, and migration, whereas PFKFB4 is involved in the drug resistance and cancer stemness of OSCC cells. Furthermore, oral cancer patients with co-expressions of PFKFB3/cell cycle or EMT markers and PFKFB4/stemness markers had poor prognosis. Conclusions PFKFB3 and PFKFB4 play different biological roles in OSCC cells, which implying that they might be potential prognostic biomarkers for OSCC patients with certain clinicopathological outcomes.

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Section: Discussionmentioning

confidence: 99%

Comparative clinical significance and biological roles of PFKFB family members in oral squamous cell carcinoma

Hu,

Shu,

Lee

et al. 2023

Cancer Cell Int

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“…Moreover, Jiajia Li et al. ( 52 ) have discovered that 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3) was correlated with lymphangiogenesis in OSCC, PFKFB3 may promote LNM by regulating the expression of podoplanin (PDPN). However, the real role of PFKFB3 in lymphangiogenesis remains need further researches ( 52 ).…”

Section: The Lymph Node Pre-metastatic Niche Formation In Hnsccmentioning

confidence: 99%

The Regulation of Lymph Node Pre-Metastatic Niche Formation in Head and Neck Squamous Cell Carcinoma

Huang

Sun

2022

Front. Oncol.

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In many distinct forms of malignancies, there is a close relationship between lymph node (LN) metastases and further dissemination to distant organs, and this is a critical prognostic factor. At the beginning of the process, the original tumor secretes soluble substances or releases extracellular vesicles (EVs) that are carried through lymphatic channels to draining (sentinel) LN. The tumor-derived factors then drive LN remodeling. These significant alterations occur prior to the emergence of the first metastatic cell, bringing about the development of a pre-metastatic niche that allows metastatic cells to survive and thrive. In this review, we discuss current information available about the regulation of lymph node pre-metastatic niche in head and neck squamous cell carcinoma (HNSCC), and the role of EVs in forming the pre-metastatic niche.

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“…Podoplanin (PDPN), a mucin‐type transmembrane protein, is conserved in different species (Astarita et al., 2012 ). Reportedly, PDPN is not only expressed in various normal cells like type I alveolar epithelial cell (Rishi et al., 1995 ), lymphatic endothelium and kidney podocytes (Koop et al., 2008 ; Wetterwald et al., 1996 ), but also frequently upregulated in numerous malignant tumours, including hypopharyngeal cancer (Wang et al., 2017 ) and squamous cell carcinoma (Li & Tang, 2021 ; Schwab et al., 2021 ), as well as in tumour stroma‐containing cancer‐associated fibroblasts (CAFs) (Jsa et al., 2020). Therefore, PDPN performs an active role in organ development, cell movement and oncogenesis.…”

Section: Introductionmentioning

confidence: 99%

Podoplanin promotes the carcinogenicity of gastric cancer by activating ezrin and mediating the crosstalk between tumour cells and cancer‐associated fibroblasts

Tian

Chen

Wang

et al. 2023

Experimental Physiology

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New Findings What is the central question of this study?To reveal the role and biological mechanism of PDPN in the progression of gastric cancer. What is the main finding and its importance?This study focused on a prognostic predictor, PDPN, which acted as a promoter in the progression of gastric cancer through the activation of Ezrin expression and CAFs. This finding may expand a new route for the gene‐targeted therapy in gastric cancer. Abstract Gastric cancer (GC) is a frequent malignant disease and the main cause of cancer‐related death in the world. Podoplanin (PDPN) has been proved to be involved in the progression of various cancers. However, the role and biological mechanism of PDPN in GC are still vague. In our study, we detected the expression of PDPN in GC tissues and cell lines using RT‐qPCR, western blot and datasets. The overall survival of GC patients was analysed with a Kaplan–Meier plot. The effects of PDPN overexpression and silencing on GC cell progression were assessed by Cell Counting Kit‐8, flow cytometry and a wound healing assay. Besides, the modulation of PDPN on ezrin activation was investigated. We further explored the role of PDPN in the crosstalk between GC cells and cancer associated fibroblasts (CAFs). Results showed that PDPN was upregulated in GC tissues and cell lines. High expression of PDPN was correlated with poor prognosis of GC patients. PDPN positively regulated the viability, migration and invasion, but inhibited apoptosis, of GC cells by mediating the activation of ezrin. Meanwhile, the change in PDPN in GC cells activated CAFs and promoted the production of cytokines secreted by CAFs, which induced the progression of GC cells. These findings may provide a novel target for GC therapy.

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Increased expression of PFKFB3 in oral squamous cell carcinoma and its association with lymphangiogenesis

Cited by 4 publications

References 36 publications

Comparative clinical significance and biological roles of PFKFB family members in oral squamous cell carcinoma

Comparative clinical significance and biological roles of PFKFB family members in oral squamous cell carcinoma

The Regulation of Lymph Node Pre-Metastatic Niche Formation in Head and Neck Squamous Cell Carcinoma

Podoplanin promotes the carcinogenicity of gastric cancer by activating ezrin and mediating the crosstalk between tumour cells and cancer‐associated fibroblasts

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