Редактирование: FASN (раздел)

==Publications==

{{medline-entry
|title=Expression of lipogenic markers is decreased in subcutaneous adipose tissue and adipocytes of older women and is negatively linked to [[GDF15]] expression.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/30912009
|abstract=In aging, the capacity of subcutaneous adipose tissue (SAT) to store lipids decreases and this results in metabolically unfavorable fat redistribution. Triggers of this age-related SAT dysfunction may include cellular senescence or endoplasmic reticulum (ER) stress. Therefore, we compared lipogenic capacity of SAT between young and older women and investigated its relation to senescence and ER stress markers. Samples of SAT and corresponding SAT-derived primary preadipocytes were obtained from two groups of women differing in age (36 vs. 72 years, n = 15 each) but matched for fat mass. mRNA levels of selected genes (lipogenesis: [[ACACA]], [[FASN]], SCD1, [[DGAT2]], ELOVL6; senescence: p16, p21, [[NOX4]], [[GDF15]]; ER stress-[[ATF4]], XBP1s, PERK, [[HSPA5]], GADD34, [[HYOU1]], CHOP, [[EDEM1]], DNAJC3) were assessed by qPCR, protein levels of [[GDF15]] by ELISA, and mitochondrial function by the Seahorse Analyzer. Compared to the young, SAT and in vitro differentiated adipocytes from older women exhibited reduced mRNA expression of lipogenic enzymes. Out of analyzed senescence and ER stress markers, the only gene, whose expression correlated negatively with the expression of lipogenic enzymes in both SAT and adipocytes, was [[GDF15]], a marker of not only senescence but also mitochondrial dysfunction. In line with this, inhibition of mitochondrial ATP synthase in adipocytes strongly upregulated [[GDF15]] while reduced expression of lipogenic enzymes. Moreover, adipocytes from older women had a tendency for diminished mitochondrial capacity. Thus, a reduced lipogenic capacity of adipocytes in aged SAT appears to be linked to mitochondrial dysfunction rather than to ER stress or accumulation of senescent cells.
|mesh-terms=* Adipocytes
* Adult
* Aged
* Aging
* Biomarkers
* Cell Differentiation
* Cellular Senescence
* Endoplasmic Reticulum Stress
* Female
* Growth Differentiation Factor 15
* Humans
* Lipogenesis
* Mitochondria
* Subcutaneous Fat
|keywords=* Aging
* Lipogenesis
* Mitochondrial dysfunction
* Senescence
* Stress of endoplasmic reticulum
* Subcutaneous adipose tissue
|full-text-url=https://sci-hub.do/10.1007/s13105-019-00676-6
}}
{{medline-entry
|title=Fatty acid synthase is a metabolic marker of cell proliferation rather than malignancy in ovarian cancer and its precursor cells.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/25302649
|abstract=Ovarian cancer (OC) is caused by genetic aberrations in networks that control growth and survival. Importantly, aberrant cancer metabolism interacts with oncogenic signaling providing additional drug targets. Tumors overexpress the lipogenic enzyme fatty acid synthase ([[FASN]]) and are inhibited by [[FASN]] blockers, whereas normal cells are [[FASN]]-negative and [[FASN]]-inhibitor-resistant. Here, we demonstrate that this holds true when ovarian/oviductal cells reside in their autochthonous tissues, whereas in culture they express [[FASN]] and are [[FASN]]-inhibitor-sensitive. Upon subculture, nonmalignant cells cease growth, express senescence-associated β-galactosidase, lose [[FASN]] and become [[FASN]]-inhibitor-resistant. Immortalized ovarian/oviductal epithelial cell lines—although resisting senescence—reveal distinct growth activities, which correlate with [[FASN]] levels and [[FASN]] drug sensitivities. Accordingly, ectopic [[FASN]] stimulates growth in these cells. Moreover, [[FASN]] levels and lipogenic activities affect cellular lipid composition as demonstrated by thin-layer chromatography. Correlation between proliferation and [[FASN]] levels was finally evaluated in cancer cells such as HOC-7, which contain subclones with variable differentiation/senescence and corresponding [[FASN]] expression/[[FASN]] drug sensitivity. Interestingly, senescent phenotypes can be induced in parental HOC-7 by differentiating agents. In OC cells, [[FASN]] drugs induce cell cycle blockade in S and/or G2/M and stimulate apoptosis, whereas in normal cells they only cause cell cycle deceleration without apoptosis. Thus, normal cells, although growth-inhibited, may survive and recover from [[FASN]] blockade, whereas malignant cells get extinguished. [[FASN]] expression and [[FASN]] drug sensitivity are directly linked to cell growth and correlate with transformation/differentiation/senescence only indirectly. [[FASN]] is therefore a metabolic marker of cell proliferation rather than a marker of malignancy and is a useful target for future drug development.
|mesh-terms=* Antineoplastic Agents
* Apoptosis
* Biomarkers, Tumor
* Cell Cycle
* Cell Line
* Cell Line, Tumor
* Cell Proliferation
* Epithelial Cells
* Fatty Acid Synthase, Type I
* Female
* Humans
* Ovarian Neoplasms
|keywords=* fallopian tube secretory epithelial cells
* fatty acid synthase
* ovarian cancer
* ovarian surface epithelial cells
* senescence
|full-text-url=https://sci-hub.do/10.1002/ijc.29261
}}
{{medline-entry
|title=Age and space irradiation modulate tumor progression: implications for carcinogenesis risk.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/23289386
|abstract=Age plays a major role in tumor incidence and is an important consideration when modeling the carcinogenesis process or estimating cancer risks. Epidemiological data show that from adolescence through middle age, cancer incidence increases with age. This effect is commonly attributed to a lifetime accumulation of cellular, particularly DNA, damage. However, during middle age the incidence begins to decelerate and, for many tumor sites, it actually decreases at sufficiently advanced ages. We investigated if the observed deceleration and potential decrease in incidence could be attributed to a decreased capacity of older hosts to support tumor progression, and whether HZE [high atomic number (Z), high energy (E)] radiation differentially modulates tumor progression in young vs. middle-age hosts, issues that are relevant to estimating carcinogenesis risk for astronauts. Lewis lung carcinoma (LLC) cells were injected into syngeneic mice (143 and 551 days old), which were then subject to whole-body (56)Fe irradiation (1 GeV/amu). Three findings emerged: (1) among unirradiated animals, substantial inhibition of tumor progression and significantly decreased tumor growth rates were seen for middle-aged mice compared to young mice, (2) whole-body (56)Fe irradiation inhibited tumor progression in both young and middle-aged mice (with greater suppression seen in case of young animals), with little effect on tumor growth rates, and (3) (56)Fe irradiation suppressed tumor progression in young mice to a degree that was not significantly different than transiting from young to middle-aged. Thus, (56)Fe irradiation acted similar to aging with respect to tumor progression. We further investigated the molecular underpinnings driving the radiation modulation of tumor dynamics in young and middle-aged mice. Through global gene expression analysis, the key players, [[FASN]], [[AKT1]] and the CXCL12/CXCR4 complex, were determined to be contributory. In sum, these findings demonstrated a reduced capacity of middle-aged hosts to support the progression phase of carcinogenesis and identify molecular factors that contribute to HZE radiation modulation of tumor progression as a function of age.
|mesh-terms=* Aging
* Animals
* Biomarkers, Tumor
* Cell Line, Tumor
* Cell Proliferation
* Disease Progression
* Extraterrestrial Environment
* Iron
* Male
* Mice
* Mice, Inbred C57BL
* Neoplasms, Radiation-Induced
* Protein Interaction Maps
* Risk
* Transcriptome
* Tumor Burden

|full-text-url=https://sci-hub.do/10.1667/RR3100.1
}}