Serum proteome‐wide identified ATP citrate lyase as a novel informative diagnostic and prognostic biomarker in pediatric sepsis: A pilot study

AbstractMetastasis is the predominant reason for high mortality of hepatocellular carcinoma (HCC) patients. It is critical to explore the molecular mechanism underlying HCC metastasis. Here, we reported that transcription factor One Cut homeobox 2 (ONECUT2) functioned as an oncogene to facilitate HCC metastasis. Elevated ONECUT2 expression was positively correlated with increased tumor number, tumor encapsulation loss, microvascular invasion, poor tumor differentiation, and advanced TNM stage. Mechanistically, ONECUT2 directly bound to the promoters of fibroblast growth factor 2 (FGF2) and ATP citrate lyase (ACLY) and transcriptionally upregulated their expression. Knockdown of FGF2 and ACLY inhibited ONECUT2-mediated HCC metastasis, whereas upregulation of FGF2 and ACLY rescued ONECUT2 knockdown-induced suppression of HCC metastasis. ONECUT2 expression was positively correlated with FGF2 and ACLY expression in human HCC tissues. HCC patients with positive coexpression of ONECUT2/FGF2 or ONECUT2/ACLY exhibited the worst prognosis. In addition, FGF2 upregulated ONECUT2 expression through the FGFR1/ERK/ELK1 pathway, which formed an FGF2-FGFR1-ONECUT2 positive feedback loop. Knockdown of ONECUT2 inhibited FGF2-induced HCC metastasis. Furthermore, the combination of FGFR1 inhibitor PD173074 with ACLY inhibitor ETC-1002 markedly suppressed ONECUT2-mediated HCC metastasis. In summary, ONECUT2 was a potential prognostic biomarker in HCC and targeting this oncogenic signaling pathway may provide an efficient therapeutic strategy against HCC metastasis.

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Cloning and Expression Analysis of ATP-Citrate Lyase Genes from Sugarcane

ACTA AGRONOMICA SINICA ◽

10.3724/sp.j.1006.2012.02024 ◽

2013 ◽

Vol 38 (11) ◽

pp. 2024-2033 ◽

Cited By ~ 3

Author(s):

Chang-Ning LI ◽

Qian NONG ◽

Qin-Liang TAN ◽

SRIVASTAVA Manoj Kumar ◽

Li-Tao YANG ◽

...

Keyword(s):

Expression Analysis ◽

Cloning And Expression ◽

Atp Citrate Lyase ◽

Citrate Lyase

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Acetyl-CoA is produced by the citrate synthase homology module of ATP-citrate lyase

Nature Structural & Molecular Biology ◽

10.1038/s41594-021-00624-3 ◽

2021 ◽

Author(s):

Kenneth Verstraete ◽

Koen H. G. Verschueren ◽

Ann Dansercoer ◽

Savvas N. Savvides

Keyword(s):

Citrate Synthase ◽

Atp Citrate Lyase ◽

Acetyl Coa ◽

Citrate Lyase ◽

Homology Module

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IGF1-mediated HOXA13 overexpression promotes colorectal cancer metastasis through upregulating ACLY and IGF1R

Cell Death and Disease ◽

10.1038/s41419-021-03833-2 ◽

2021 ◽

Vol 12 (6) ◽

Author(s):

Chenyang Qiao ◽

Wenjie Huang ◽

Jie Chen ◽

Weibo Feng ◽

Tongyue Zhang ◽

...

Keyword(s):

Colorectal Cancer ◽

Growth Factor ◽

Cancer Metastasis ◽

Combined Treatment ◽

Insulin Like Growth Factor ◽

Atp Citrate Lyase ◽

Citrate Lyase ◽

Elevated Expression ◽

Igf1r Inhibitor ◽

Colorectal Cancer Metastasis

AbstractMetastasis is the major reason for the high mortality of colorectal cancer (CRC) patients and its molecular mechanism remains unclear. Here, we report a novel role of Homeobox A13 (HOXA13), a member of the Homeobox (HOX) family, in promoting CRC metastasis. The elevated expression of HOXA13 was positively correlated with distant metastasis, higher AJCC stage, and poor prognosis in two independent CRC cohorts. Overexpression of HOXA13 promoted CRC metastasis whereas downregulation of HOXA13 suppressed CRC metastasis. Mechanistically, HOXA13 facilitated CRC metastasis by transactivating ATP-citrate lyase (ACLY) and insulin-like growth factor 1 receptor (IGF1R). Knockdown of ACLY and IGFIR inhibited HOXA13-medicated CRC metastasis, whereas ectopic overexpression of ACLY and IGFIR rescued the decreased CRC metastasis induced by HOXA13 knockdown. Furthermore, Insulin-like growth factor 1 (IGF1), the ligand of IGF1R, upregulated HOXA13 expression through the PI3K/AKT/HIF1α pathway. Knockdown of HOXA13 decreased IGF1-mediated CRC metastasis. In addition, the combined treatment of ACLY inhibitor ETC-1002 and IGF1R inhibitor Linsitinib dramatically suppressed HOXA13-mediated CRC metastasis. In conclusion, HOXA13 is a prognostic biomarker in CRC patients. Targeting the IGF1-HOXA13-IGF1R positive feedback loop may provide a potential therapeutic strategy for the treatment of HOXA13-driven CRC metastasis.

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