ArticleJournal of experimental & clinical cancer research : CR2016
FLIP(L) is critical for aerobic glycolysis in hepatocellular carcinoma.
Article in Journal of experimental & clinical cancer research : CR, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 19 citations in OpenAlex.
- M6A-modified BFSP1 induces aerobic glycolysis to promote liver cancer growth and metastasis through upregulating tropomodulin 4.Molecular biomedicine · 2025Article
- YY1 transcription factor induces proliferation and aerobic glycolysis of neuroblastoma cells via LDHA regulation.Experimental and therapeutic medicine · 2023Article
- c-FLIP promotes drug resistance in non-small-cell lung cancer cells via upregulating FoxM1 expression.Acta pharmacologica Sinica · 2022Article
- Construction of a predictive nomogram and bioinformatic investigation of the potential mechanism of postoperative early recurrence of hepatocellular carcinoma meeting the Milan criteria.Annals of translational medicine · 2022Article
- A risk model of gene signatures for predicting platinum response and survival in ovarian cancer.Journal of ovarian research · 2022Article
- Glucose transporters as markers of diagnosis and prognosis in cancer diseases.Oncology reviews · 2022Article
- Oncogenic signaling inhibits c-FLIPScientific reports · 2021Article
- The EGFR-P38 MAPK axis up-regulates PD-L1 through miR-675-5p and down-regulates HLA-ABC via hexokinase-2 in hepatocellular carcinoma cells.Cancer communications (London, England) · 2021Article
- Dynamic Changes of Urine Proteome in Rat Models Inoculated with Two Different Hepatoma Cell Lines.Journal of oncology · 2021Article
- The landscape of tumors-infiltrate immune cells in papillary thyroid carcinoma and its prognostic value.PeerJ · 2021Article
- FLIP(L): the pseudo-caspase.The FEBS journal · 2020Review
- SLC5A1 promotes growth and proliferation of pancreatic carcinoma via glucose-dependent AMPK/mTOR signaling.Cancer management and research · 2019Article
- Multiple Functions of Cellular FLIP Are Essential for Replication of Hepatitis B Virus.Journal of virology · 2018Article
- Molecular Targets in Hepatocarcinogenesis and Implications for Therapy.Journal of clinical medicine · 2018Review
- Silencing the Girdin gene enhances radio-sensitivity of hepatocellular carcinoma via suppression of glycolytic metabolism.Journal of experimental & clinical cancer research : CR · 2017Article
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundTumor cells use aerobic glycolysis to rapidly generate ATP and growth substrate which expenses a large amount of glucose. However, how tumor cells take in enough glucose from the tumor microenvironment of insufficient blood supply remains poorly understood. The cellular FLICE-like inhibitory protein (FLIP), a cell apoptosis inhibiting molecule, is highly expressed in hepatocellular carcinoma (HCC) and is implicated in HCC development.
methodsThe effects of FLIPL (the long form of FLIP) on aerobic glycolysis and glucose uptake were assessed in HCC cells and xenograft tumors. The correlations between FLIPL expression and sodium/glucose cotransporter 1 (SGLT1) expression in clinical HCC tissues were analyzed. The consequences of FLIPL-induced regulation of SGLT1 at the transcription and translation levels and the interaction between FLIPL and SGLT1 were examined. FLIPL-mediated tolerance upon glucose limitation and its mechanism were detected.
resultsWe report a novel role for FLIPL in promoting the aerobic glycolysis of HCC cells. FLIPL overexpression induced a significant increase in cell aerobic glycolysis indexes including glucose uptake, glucose consumption, and lactate production. FLIPL co-localized and interacted with SGLT1, a major active glucose transporter in HCC cells. FLIPL increased the stability of SGLT1 protein by inhibiting its ubiquitination and degradation. The expression level of FLIPL was positively correlated with the expression level of SGLT1 in 79 HCC tissues from surgical operation. Furthermore, FLIPL increased cell tolerance ability and decreased cell apoptosis to low glucose by regulating SGLT1.
conclusionsOur results indicate that FLIPL plays an essential role in HCC aerobic glycolysis and that SGLT1 is required for FLIPL-modulated tumor proliferation under low glucose conditions. Targeting the actions of FLIPL in cell glucose-dependent aerobic glycolysis may provide an attractive strategy for therapeutic intervention in HCC.
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