INT343192

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Context Info
Confidence 0.75
First Reported 2010
Last Reported 2010
Negated 0
Speculated 0
Reported most in Body
Documents 1
Total Number 46
Disease Relevance 20.21
Pain Relevance 0.35

This is a graph with borders and nodes. Maybe there is an Imagemap used so the nodes may be linking to some Pages.

mitochondrion (ACSL4) small molecule metabolic process (ACSL4) endoplasmic reticulum (ACSL4)
peroxisome (ACSL4) ligase activity (ACSL4)
Anatomy Link Frequency
MCF-7 14
colon 7
MDA-MB-231 4
liver 2
ACSL4 (Homo sapiens)
Pain Link Frequency Relevance Heat
cINOD 46 99.16 Very High Very High Very High
COX-2 inhibitor 46 91.28 High High
COX2 46 30.92 Quite Low
Disease Link Frequency Relevance Heat
Breast Cancer 1702 99.96 Very High Very High Very High
Colon Cancer 414 99.86 Very High Very High Very High
Cancer 644 99.80 Very High Very High Very High
Aggression 276 99.68 Very High Very High Very High
INFLAMMATION 46 99.04 Very High Very High Very High
Hepatocellular Cancer 230 98.88 Very High Very High Very High
Apoptosis 552 98.84 Very High Very High Very High
Injury 966 97.36 Very High Very High Very High
Liver Cancer 46 96.52 Very High Very High Very High
Hyperplasia 46 90.00 High High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
Therefore, it is important to determine the role and molecular mechanism that govern the relationship between ACSL4 expression and the metabolic pathway of AA in cancer cells.
Gene_expression (expression) of ACSL4 associated with cancer
1) Confidence 0.75 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2978721 Disease Relevance 1.18 Pain Relevance 0
Interestingly, neither overexpression nor inhibition of ACOT2 expression in MCF-7, a cell that expresses low amounts of ACSL4, has an effect on cell proliferation.
Gene_expression (expresses) of ACSL4 in MCF-7
2) Confidence 0.75 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2978721 Disease Relevance 0.26 Pain Relevance 0
Increased ACSL4 expression, both at mRNA and protein levels [3], in colon adenocarcinoma cells has been associated with inhibition of apoptosis and increase in cell proliferation when compared to adjacent normal tissue.
Gene_expression (expression) of ACSL4 in colon associated with colon cancer and apoptosis
3) Confidence 0.75 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2978721 Disease Relevance 0.74 Pain Relevance 0
However, overexpression of ACSL4 resulted in slight by not statistically significant increase in 5-LOX expression (data not shown).
Gene_expression (overexpression) of ACSL4
4) Confidence 0.75 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2978721 Disease Relevance 0.48 Pain Relevance 0
It can therefore be argued that ACSL4 overexpression might contribute to the development of an aggressive phenotype in breast cancer cells by regulating the production of lipooxygenase and cyclooxygenase metabolites.
Gene_expression (overexpression) of ACSL4 associated with breast cancer
5) Confidence 0.75 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2978721 Disease Relevance 0.80 Pain Relevance 0.08
Consequently, transient transfection of the low aggressive phenotype and low-level expression of ACSL4 cell line, MCF-7, with the full length human ACSL4 cDNA resulted in increased aggressiveness of the cells manifested as augmented cell proliferation, invasion and migration.
Gene_expression (expression) of ACSL4 in MCF-7 associated with aggression
6) Confidence 0.75 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2978721 Disease Relevance 0.58 Pain Relevance 0
The formation of 5-, 12-, and 15-LOX products was significantly increased in cells overexpressing ACSL4 than in cells treated with tetracycline (Fig. 6C).
Gene_expression (overexpressing) of ACSL4
7) Confidence 0.75 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2978721 Disease Relevance 0.48 Pain Relevance 0
In this system, further functional studies were performed to confirm whether an increased ACSL4 expression may lead to increased cell proliferation and migration as described above.
Gene_expression (expression) of ACSL4
8) Confidence 0.75 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2978721 Disease Relevance 0.26 Pain Relevance 0
In parallel with the expression of ACSL4 and ACOT2, intramitochondrial AA levels were significantly higher in MDA-MB-231 than in MCF-7 cells (Fig. 4B).
Gene_expression (expression) of ACSL4 in MDA-MB-231
9) Confidence 0.75 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2978721 Disease Relevance 0.27 Pain Relevance 0
The tetracycline-repressible MCF-7 cell line, designated MCF-7 Tet-off, was used for stably transfection of ACSL4 cDNA under control of the tetracycline-response element using the Tet-Off Gene Expression System (Clontech).
Gene_expression (transfection) of ACSL4 cDNA in MCF-7
10) Confidence 0.75 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2978721 Disease Relevance 0.07 Pain Relevance 0
After several weeks, colonies in which the expressed ACSL4 was regulated by tetracycline (2 µg/ml) were selected, cultured and subjected to different functional assays.
Gene_expression (expressed) of ACSL4
11) Confidence 0.75 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2978721 Disease Relevance 0.09 Pain Relevance 0
Previous investigations in colon adenocarcinoma or hepatocellular cells reported that ACSL4 overexpression or inhibition associated only with increased or decreased cell proliferation respectively [3], [4], [6], [21], [38].
Gene_expression (overexpression) of ACSL4 in colon associated with colon cancer
12) Confidence 0.75 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2978721 Disease Relevance 0.80 Pain Relevance 0.05
However, the phenotype was changed by both overexpression and knockdown of ACOT2 in MDA-MB-231 cells that express high levels of ACSL4.
Gene_expression (express) of ACSL4 in MDA-MB-231
13) Confidence 0.75 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2978721 Disease Relevance 0.09 Pain Relevance 0
Moreover, in colon adenocarcinoma where ACSL4 expression is associated with an increased proliferation rate, ACSL1 expression was not changed or was even down-regulated [3].
Gene_expression (expression) of ACSL4 in colon associated with colon cancer
14) Confidence 0.75 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2978721 Disease Relevance 0.46 Pain Relevance 0
In line with these results, inhibition of ACSL4 expression in the highly aggressive and high-level expression of ACSL4 cell line, MDA-MB-231, by transfection of a plasmid containing ACSL4-shRNA resulted in decreased aggresiveness.
Gene_expression (expression) of ACSL4 in MDA-MB-231
15) Confidence 0.75 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2978721 Disease Relevance 0.62 Pain Relevance 0
We therefore investigated COX-2 expression levels in the breast cancer cell model used for ACSL4 expression studies.
Gene_expression (expression) of ACSL4 associated with breast cancer
16) Confidence 0.75 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2978721 Disease Relevance 0.46 Pain Relevance 0
Another significant finding was that intramitochondrial AA levels were significantly increased in MDA-MB-231 cells as compared to those in MCF-7 cells and that increased AA levels correlated with higher expression levels of ACSL4.
Gene_expression (expression) of ACSL4 in MCF-7
17) Confidence 0.75 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2978721 Disease Relevance 0.61 Pain Relevance 0
The involvement of ACSL4 in the regulation of intramitochondrial AA levels and lipooxygenase products were confirmed by inhibition of ACSL4 expression and the use of the MCF-7 Tet-off/ACSL4 transfection approach.
Gene_expression (expression) of ACSL4 in MCF-7
18) Confidence 0.75 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2978721 Disease Relevance 0.39 Pain Relevance 0
The finding that tetracycline abolished the difference in the aggressive phenotype of MCF-7 Tet-off/ACSL4 cells strongly indicates that the increase in cell proliferation, invasion and migration were a direct result of the increased ACSL4 expression.
Gene_expression (expression) of ACSL4 in MCF-7
19) Confidence 0.75 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2978721 Disease Relevance 0.53 Pain Relevance 0
This might bring about a common mechanism, at least in tumors known to express high amounts of ACSL4, such as breast, colon and hepatocellular carcinoma, where its high expression is associated with tumorigenesis.


Gene_expression (express) of ACSL4 in colon associated with cancer and hepatocellular cancer
20) Confidence 0.75 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2978721 Disease Relevance 0.72 Pain Relevance 0.07

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