The FOXC1/FBP1 signaling axis promotes colorectal cancer proliferation by enhancing the Warburg effect

Li, Qingguo; Wei, Ping; Wu, Jitao; Zhang, Meng; Li, Guichao; Li, Yaqi; Xu, Ye; Li, Xinxiang; Xie, Dacheng; Cai, Sanjun; Xie, Keping; Li, Dawei

doi:10.1038/s41388-018-0469-8

Cited by 52 publications

(58 citation statements)

References 54 publications

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“…IHC study was used to explore S100A4 expression in patients as previously described [8] . Primary anti-S100A4 antibody (ab124805, 1:1000; Abcam) and goat anti-rabbit Envision System Plus-HRP (Dako Cytomation) were used for the study.…”

Section: Ihc Analysismentioning

confidence: 99%

“…Fast Real-Time PCR System (Applied Biosystems, Foster City, CA, USA) as previous described [8,19] . All primers were listed in Table 1.β-actin was used as an internal control.…”

Section: Rna Isolation and Qpcr Assaymentioning

confidence: 99%

“…Standard Western blotting was carried out as previous described [8,20] . Primary antibodies anti-S100A4 (ab124805, 1:1000; Abcam), or anti-β-actin (ab133626, 1:5000; Abcam) and secondary antibodies (anti-rabbit IgG; Cell Signaling Technology, Danvers, MA, USA) were used.…”

Section: Western Blottingmentioning

confidence: 99%

“…The glucose assay kit (BioVision, Milpitas, CA, USA) was used to detect relative glucose uptake and lactate production among different S100A4 expression groups in CRC cells. All reactions were 5 performed in triplicate as described previously [8] .…”

Section: Glucose Uptake and Lactate Production Assaysmentioning

confidence: 99%

“…Because it is closely related with increased progression and metastasis abilities of cancer, aerobic glycolysis is one of the basic characteristics of invasive tumors [4,5] . Recently, studies have revealed that genetic or epigenetic changes in oncogenes or tumor suppressors lead to activation of glycolysis, as most glycolytic enzymes are regulated by oncogenes or tumor suppressors such as hypoxia inducible factor (HIF) [6] , Myc [7] , FOXC1 [8] , FOXM1 [9] , Gas1 [5] , et al…”

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confidence: 99%

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S100A4 promotes colorectal carcinoma growth by enhancing aerobic glycolysis

et al. 2020

Preprint

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Background Glucose metabolism transformation plays critical role in cancer cell malignancies maintenance. Aberrant cancer cell metabolism is considered to be the hallmark of cancer. S100A4 has been identified as an oncogene in a variety of cancers. However, its role in the cancer cell glucose reprogramming has been seldom reported. The aim of this study was to examine the role of S100A4 in aerobic glycolysis in colorectal cancer (CRC). Methods We investigated S100A4 expression in 224 cases of primary CRC and matched normal colonic tissue specimens, and explored the underlying mechanisms of altered S100A4 expression as well as the impact of this altered expression on CRC growth and glycolysis using in vitro and animal models of CRC. Results S100A4 was more highly expressed in CRC tissues than in the adjacent normal tissues (59.4% vs 17.4%, P <0.05). Higher S100A4 expression was associated with advanced node stage ( P =0.018) and larger tumor size ( P =0.035). A Cox proportional hazards model suggested that S100A4 expression was an independent prognostic factor for both OS (HR: 3.967, 95%CI: 1.919-8.200, P <0.001) and DFS (HR: 4.350, 95%CI: 2.264-8.358, P <0.001) in CRC after surgery. Experimentally, silencing S100A4 expression significantly decreased the growth and glycolysis rate of CRC both in vitro and in vivo . Mechanically, S100A4 could affect the hypoxia-inducible factor (HIF)-1α activity as demonstrated by the HIF-1α response element–luciferase activity in CRC cells. Conclusions These results disclose a novel role for S100A4 in reprogramming the metabolic process in CRC by affecting the HIF-1α activity and provide potential prognostic predictors for CRC.

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Section: Ihc Analysismentioning

confidence: 99%

“…Fast Real-Time PCR System (Applied Biosystems, Foster City, CA, USA) as previous described [8,19] . All primers were listed in Table 1.β-actin was used as an internal control.…”

Section: Rna Isolation and Qpcr Assaymentioning

confidence: 99%

Section: Western Blottingmentioning

confidence: 99%

Section: Glucose Uptake and Lactate Production Assaysmentioning

confidence: 99%

mentioning

confidence: 99%

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S100A4 promotes colorectal carcinoma growth by enhancing aerobic glycolysis

et al. 2020

Preprint

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Construction of a prognostic glycolysis‐related lncRNA signature for patients with colorectal cancer

Zhong

Wang

et al. 2022

Cancer Medicine

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Aerobic glycolysis is a common metabolic phenotype in tumors that helps cancer cells adjust to severe living conditions and can aid metastasis in several types of carcinomas, including colorectal cancer (CRC). Long non‐coding RNAs (lncRNAs) can influence tumor biology and have been previously used to assess patients' outcomes and to identify potential therapeutic targets. However, despite the importance of glycolysis‐related lncRNAs (GRLs) in the development of CRC, studies on their use as prognostic markers are still limited. Herein, we applied a series of bioinformatic analyses to screen potential prognostic lncRNAs for colorectal cancer. Out of all lncRNAs screened, nine GRLs were selected to constitute a prognostic signature. Based on the signature, two molecular subtypes were classified with distinct prognostic outcomes and excellent diagnostic accuracy (The 1‐, 3‐ and 5‐year AUC are 0.756, 0.716, and 0.721, respectively). The prognostic value of this signature was further validated using another cohort. The enriched molecular pathways, immune infiltration, and mutation landscape were also significantly different between the two groups. The different drug sensitivity results between the two groups suggest a potential strategy for precise treatment. Furthermore, we confirmed that AFAP1‐AS1 could regulate aerobic glycolysis and metastasis of CRC cells. Overall, we developed a glycolysis‐related lncRNA (GRL) signature and suggested that this signature could offer a predictive value and identify potential therapeutic targets for cancer therapy.

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AF9 sustains glycolysis in colorectal cancer via H3K9ac‐mediated PCK2 and FBP1 transcription

He,

Zhong,

Fang

et al. 2023

Clinical & Translational Med

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BackgroundThe tumourigenesis of various cancers is influenced by epigenetic deregulation. Among 591 epigenetic regulator factors (ERFs) examined, AF9 showed significant inhibition of malignancy in colorectal cancer (CRC) based on our wound healing assays. However, the precise role of AF9 in CRC remains to be explored.MethodsTo investigate the function of AF9 in CRC, we utilised small interfering RNAs (siRNAs) to knock down the expression of 591 ERFs. Subsequently, we performed wound healing assays to evaluate cell proliferation and migration. In vitro and in vivo assays were conducted to elucidate the potential impact of AF9 in CRC. Clinical samples were analysed to assess the association between AF9 expression and CRC prognosis. Additionally, an Azoxymethane‐Dextran Sodium Sulfate (AOM/DSS) induced CRC AF9IEC‐/‐ mouse model was employed to confirm the role of AF9 in CRC. To identify the target gene of AF9, RNA‐seq and coimmunoprecipitation analyses were performed. Furthermore, bioinformatics prediction was applied to identify potential miRNAs that target AF9.ResultsAmong the 591 ERFs examined, AF9 exhibited downregulation in CRC and showed a positive correlation with prolonged survival in CRC patients. In vitro and in vivo assays proved that depletion of AF9 could promote cell proliferation, migration as well as glycolysis. Specifically, knockout of MLLT3 (AF9) in intestinal epithelial cells significantly increased tumour formation induced by AOM/DSS. We also identified miR‐145 could target 3′untranslated region of AF9 to suppress AF9 expression. Loss of AF9 led to decreased expression of gluconeogenic genes, including phosphoenolpyruvate carboxykinase 2 (PCK2) and fructose 1,6‐bisphosphatase 1 (FBP1), subsequently promoting glucose consumption and tumourigenesis.ConclusionsAF9 is essential for the upregulation of PCK2 and FBP1, and the disruption of the miR‐145/AF9 axis may serve as a potential target for the development of CRC therapeutics.

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The FOXC1/FBP1 signaling axis promotes colorectal cancer proliferation by enhancing the Warburg effect

Cited by 52 publications

References 54 publications

S100A4 promotes colorectal carcinoma growth by enhancing aerobic glycolysis

S100A4 promotes colorectal carcinoma growth by enhancing aerobic glycolysis

Construction of a prognostic glycolysis‐related lncRNA signature for patients with colorectal cancer

AF9 sustains glycolysis in colorectal cancer via H3K9ac‐mediated PCK2 and FBP1 transcription

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