c-Src Promotes Tumorigenesis and Tumor Progression by Activating PFKFB3

Ma, Huanhuan; Zhang, Jia; Zhou, Lin; Wen, Shixiong; Tang, Hsiang-Yu; Jiang, Bin; Zhang, Fengqiong; Suleman, Muhammad; Sun, Dao Heng; Chen, Ai; Zhao, Wentao; Lin, Furong; Tsau, Ming-Tong; Shih, Lu-Min; Xie, Changchuan; Li, Xiaotong; Lin, Donghai; Hung, Li-Man; Cheng, Mei‐Ling; Li, Qinxi

doi:10.1016/j.celrep.2020.03.005

Cited by 43 publications

(31 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The proto-oncogene, Src, has been shown to regulate glycolysis. [111][112][113] In a publication by Park et al, it was suggested that IL-32 can bind to Src in breast cancer cells. 77 The proposed mechanism was that IL-32 prolonged Src activation by protecting it from dephosphorylation by the protein phosphatase 2 (PP2A).…”

Section: Src Kinasementioning

confidence: 99%

See 1 more Smart Citation

Molecular interactions and functions of IL-32

Aass¹,

Kastnes²,

Standal

2020

Journal of Leukocyte Biology

View full text Add to dashboard Cite

IL-32 is a multifaceted cytokine associated with several diseases and inflammatory conditions. Its expression is induced in response to cellular stress such as hypoxia, infections, and proinflammatory cytokines. IL-32 can be secreted from cells and can induce the production of proinflammatory cytokines from several cell types but are also described to have anti-inflammatory functions. The intracellular form of IL-32 is shown to play an important role in various cellular processes, including the defense against intracellular bacteria and viruses and in modulation of cell metabolism. In this review, we discuss current literature on molecular interactions of IL-32 with other proteins. We also review data on the role of intracellular IL-32 as a metabolic regulator and its role in antimicrobial host defense.

show abstract

Section: Src Kinasementioning

confidence: 99%

“…The proto‐oncogene, Src, has been shown to regulate glycolysis 111–113 . In a publication by Park et al., it was suggested that IL‐32β can bind to Src in breast cancer cells 77 .…”

Section: Il‐32 Receptor(s) and Binding Partnersmentioning

confidence: 99%

Molecular interactions and functions of IL-32

Aass¹,

Kastnes²,

Standal

2020

Journal of Leukocyte Biology

View full text Add to dashboard Cite

show abstract

“…Third, Src can respond to the strong tumour energy demand by phosphorylating and activating several metabolic cascades. For instance, Src can promote intestinal tumour development by direct phosphorylation of the glycolytic enzyme PFKFBP3 enabling aberrant anabolic glycolysis [ 112 ]. Src may deregulate mTORC1 activity, a master regulator of protein synthesis, by overriding its inhibition by Gator1 [ 113 ].…”

Section: Sfks In Human Crcmentioning

confidence: 99%

Src Family Tyrosine Kinases in Intestinal Homeostasis, Regeneration and Tumorigenesis

Sirvent

Mevizou

Naim

et al. 2020

Cancers

View full text Add to dashboard Cite

Src, originally identified as an oncogene, is a membrane-anchored tyrosine kinase and the Src family kinase (SFK) prototype. SFKs regulate the signalling induced by a wide range of cell surface receptors leading to epithelial cell growth and adhesion. In the intestine, the SFK members Src, Fyn and Yes regulate epithelial cell proliferation and migration during tissue regeneration and transformation, thus implicating conserved and specific functions. In patients with colon cancer, SFK activity is a marker of poor clinical prognosis and a potent driver of metastasis formation. These tumorigenic activities are linked to SFK capacity to promote the dissemination and tumour-initiating capacities of epithelial tumour cells. However, it is unclear how SFKs promote colon tumour formation and metastatic progression because SFK-encoding genes are unfrequently mutated in human cancer. Here, we review recent findings on SFK signalling during intestinal homeostasis, regeneration and tumorigenesis. We also describe the key nongenetic mechanisms underlying SFK tumour activities in colorectal cancer, and discuss how these mechanisms could be exploited in therapeutic strategies to target SFK signalling in metastatic colon cancer.

show abstract

“…Most of the literature has reported that increasing PFKFB3 promotes tumorigenesis and proliferation [20][21][22]. However, experiment result in astrocytoma cells is inconsistent.…”

Section: Discussionmentioning

confidence: 99%

Overexpression of PFKFB3 Promotes Cell Glycolysis and Proliferation in Renal Cell Carcinoma

Li¹,

Zhang²,

Liao³

et al. 2021

Preprint

View full text Add to dashboard Cite

Background: Cancer cells prefer aerobic glycolysis to increase their biomass and sustain uncontrolled proliferation. As a key glycolytic activator, phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3) has been implicated in the progression of multiple types of tumors. However, the specific function and clinical significance of PFKFB3 in renal cell carcinoma (RCC) remain unclear. In the present study, we explored the role of PFKFB3 in RCC.Methods: We analyzed the expression of PFKFB3 in clear cell renal cell carcinoma (ccRCC) tissues and its relationship with clinical characteristics of ccRCC. Real-time PCR and Western blot analysis were used to detect PFKFB3 expression levels in different RCC cell lines. Furthermore, we determined the glycolytic activity by glucose uptake, lactate secretion assay and ECAR analysis. CCK-8 assay, clone formation assay, flow cytometry and EdU assay were performed to monitor cancer cell proliferation and cell cycle distribution. In addition, nude mice xenograft model was used to investigate the role of PFKFB3 in tumor growth in vivo.Results: In this study, we found that PFKFB3 was significantly up-regulated in RCC tissues and cell lines compared with normal control. Overexpression of PFKFB3 was positively associated with advanced TNM stage and could predict poor prognosis of ccRCC patients. Furthermore, knockdown of PFKFB3 suppresses cell glycolysis, proliferation and cell cycle G1/S transition in RCC cells. Importantly, in vivo experiments confirmed that PFKFB3 knockdown delayed tumor growth derived from the ACHN cell line.Conclusion: Our results suggest that PFKFB3 plays an important role in the progression of RCC via mediating glycolysis and proliferation, and provides a potential therapeutic target for RCC.

show abstract

c-Src Promotes Tumorigenesis and Tumor Progression by Activating PFKFB3

Cited by 43 publications

References 52 publications

Molecular interactions and functions of IL-32

Molecular interactions and functions of IL-32

Src Family Tyrosine Kinases in Intestinal Homeostasis, Regeneration and Tumorigenesis

Overexpression of PFKFB3 Promotes Cell Glycolysis and Proliferation in Renal Cell Carcinoma

Contact Info

Product

Resources

About