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SIRT3 Enhances Glycolysis and Proliferation in SIRT3-Expressing Gastric Cancer Cells.

Cui Y, Qin L, Wu J, Qu X, Hou C, Sun W, Li S, Vaughan AT, Li JJ, Liu J - PLoS ONE (2015)

Bottom Line: Although SIRT3 expression levels were increased in the gastric tumor tissues compared to the adjacent non-tumor tissues, SIRT3 positive cancer cells were more frequently detected in the intestinal type gastric cancers than the diffuse type gastric cancers, indicating that SIRT3 is linked with subtypes of gastric cancer.Further analysis revealed that SIRT3 interacted with and deacetylated the lactate dehydrogenase A (LDHA), a key protein in regulating anaerobic glycolysis, enhancing LDHA activity.Thus, in addition to the well-documented SIRT3-mediated mitochondrial homeostasis in normal cells, SIRT3 may enhance glycolysis and cell proliferation in SIRT3-expressing cancer cells.

View Article: PubMed Central - PubMed

Affiliation: Center for Mitochondrial Biology and Medicine, Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology and Frontier Institute of Life Science, Xi'an Jiaotong University, Xi'an, 710049, China.

ABSTRACT
SIRT3 is a key NAD+-dependent protein deacetylase in the mitochondria of mammalian cells, functioning to prevent cell aging and transformation via regulation of mitochondrial metabolic homeostasis. However, SIRT3 is also found to express in some human tumors; its role in these SIRT3-expressing tumor cells needs to be elucidated. This study demonstrated that the expression of SIRT3 was elevated in a group of gastric cancer cells compared to normal gastric epithelial cells. Although SIRT3 expression levels were increased in the gastric tumor tissues compared to the adjacent non-tumor tissues, SIRT3 positive cancer cells were more frequently detected in the intestinal type gastric cancers than the diffuse type gastric cancers, indicating that SIRT3 is linked with subtypes of gastric cancer. Overexpression of SIRT3 promoted cell proliferation and enhanced ATP generation, glucose uptake, glycogen formation, MnSOD activity and lactate production, which were inhibited by SIRT3 knockdown, indicating that SIRT3 plays a role in reprogramming the bioenergetics in gastric tumor cells. Further analysis revealed that SIRT3 interacted with and deacetylated the lactate dehydrogenase A (LDHA), a key protein in regulating anaerobic glycolysis, enhancing LDHA activity. In consistence, a cluster of glycolysis-associated genes was upregulated in the SIRT3-overexpressing gastric tumor cells. Thus, in addition to the well-documented SIRT3-mediated mitochondrial homeostasis in normal cells, SIRT3 may enhance glycolysis and cell proliferation in SIRT3-expressing cancer cells.

No MeSH data available.


Related in: MedlinePlus

Overexpression of SIRT3 enhances glycolysis in gastric cancer cells.Glucose uptake, lactate production and glycogen formation were measured in AGS (A, C, E) and SGC-7901 (B, D, F) cells with SIRT3 overexpression or knockdown. All data are presented as mean ± S.E. (n = 3; *, p < 0.05; **, p < 0.01).
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pone.0129834.g003: Overexpression of SIRT3 enhances glycolysis in gastric cancer cells.Glucose uptake, lactate production and glycogen formation were measured in AGS (A, C, E) and SGC-7901 (B, D, F) cells with SIRT3 overexpression or knockdown. All data are presented as mean ± S.E. (n = 3; *, p < 0.05; **, p < 0.01).

Mentions: We were then wondering how cellular bioenergetics could be altered in SIRT3-overexpressing gastric cancer cells. SIRT3 overexpression dramatically increased glucose uptake (1.4-fold in AGS and 1.9-fold in SGC-7901), while SIRT3 knockdown decreased glucose uptake (around 40% in both AGS and SGC-7901) (Fig 3A and 3B). Consistent with the pattern of glucose usage, SIRT3 overexpressing cells had increased levels of lactate secretion (1.2-fold in AGS and 1.3-fold in SGC-7901), whereas SIRT3 knockdown cells had decreased levels of lactate secretion (55% in AGS and 45% in SGC-7901) (Fig 3C and 3D). We also found that glycogen formation was significantly increased by SIRT3 overexpression (1.5-fold in AGS and 1.3-fold in SGC-7901), a feature of quick growth of tumor cell [33], while reduced by SIRT3 knockdown (40% in AGS and 70% in SGC-7901) (Fig 3E and 3F).


SIRT3 Enhances Glycolysis and Proliferation in SIRT3-Expressing Gastric Cancer Cells.

Cui Y, Qin L, Wu J, Qu X, Hou C, Sun W, Li S, Vaughan AT, Li JJ, Liu J - PLoS ONE (2015)

Overexpression of SIRT3 enhances glycolysis in gastric cancer cells.Glucose uptake, lactate production and glycogen formation were measured in AGS (A, C, E) and SGC-7901 (B, D, F) cells with SIRT3 overexpression or knockdown. All data are presented as mean ± S.E. (n = 3; *, p < 0.05; **, p < 0.01).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4487898&req=5

pone.0129834.g003: Overexpression of SIRT3 enhances glycolysis in gastric cancer cells.Glucose uptake, lactate production and glycogen formation were measured in AGS (A, C, E) and SGC-7901 (B, D, F) cells with SIRT3 overexpression or knockdown. All data are presented as mean ± S.E. (n = 3; *, p < 0.05; **, p < 0.01).
Mentions: We were then wondering how cellular bioenergetics could be altered in SIRT3-overexpressing gastric cancer cells. SIRT3 overexpression dramatically increased glucose uptake (1.4-fold in AGS and 1.9-fold in SGC-7901), while SIRT3 knockdown decreased glucose uptake (around 40% in both AGS and SGC-7901) (Fig 3A and 3B). Consistent with the pattern of glucose usage, SIRT3 overexpressing cells had increased levels of lactate secretion (1.2-fold in AGS and 1.3-fold in SGC-7901), whereas SIRT3 knockdown cells had decreased levels of lactate secretion (55% in AGS and 45% in SGC-7901) (Fig 3C and 3D). We also found that glycogen formation was significantly increased by SIRT3 overexpression (1.5-fold in AGS and 1.3-fold in SGC-7901), a feature of quick growth of tumor cell [33], while reduced by SIRT3 knockdown (40% in AGS and 70% in SGC-7901) (Fig 3E and 3F).

Bottom Line: Although SIRT3 expression levels were increased in the gastric tumor tissues compared to the adjacent non-tumor tissues, SIRT3 positive cancer cells were more frequently detected in the intestinal type gastric cancers than the diffuse type gastric cancers, indicating that SIRT3 is linked with subtypes of gastric cancer.Further analysis revealed that SIRT3 interacted with and deacetylated the lactate dehydrogenase A (LDHA), a key protein in regulating anaerobic glycolysis, enhancing LDHA activity.Thus, in addition to the well-documented SIRT3-mediated mitochondrial homeostasis in normal cells, SIRT3 may enhance glycolysis and cell proliferation in SIRT3-expressing cancer cells.

View Article: PubMed Central - PubMed

Affiliation: Center for Mitochondrial Biology and Medicine, Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology and Frontier Institute of Life Science, Xi'an Jiaotong University, Xi'an, 710049, China.

ABSTRACT
SIRT3 is a key NAD+-dependent protein deacetylase in the mitochondria of mammalian cells, functioning to prevent cell aging and transformation via regulation of mitochondrial metabolic homeostasis. However, SIRT3 is also found to express in some human tumors; its role in these SIRT3-expressing tumor cells needs to be elucidated. This study demonstrated that the expression of SIRT3 was elevated in a group of gastric cancer cells compared to normal gastric epithelial cells. Although SIRT3 expression levels were increased in the gastric tumor tissues compared to the adjacent non-tumor tissues, SIRT3 positive cancer cells were more frequently detected in the intestinal type gastric cancers than the diffuse type gastric cancers, indicating that SIRT3 is linked with subtypes of gastric cancer. Overexpression of SIRT3 promoted cell proliferation and enhanced ATP generation, glucose uptake, glycogen formation, MnSOD activity and lactate production, which were inhibited by SIRT3 knockdown, indicating that SIRT3 plays a role in reprogramming the bioenergetics in gastric tumor cells. Further analysis revealed that SIRT3 interacted with and deacetylated the lactate dehydrogenase A (LDHA), a key protein in regulating anaerobic glycolysis, enhancing LDHA activity. In consistence, a cluster of glycolysis-associated genes was upregulated in the SIRT3-overexpressing gastric tumor cells. Thus, in addition to the well-documented SIRT3-mediated mitochondrial homeostasis in normal cells, SIRT3 may enhance glycolysis and cell proliferation in SIRT3-expressing cancer cells.

No MeSH data available.


Related in: MedlinePlus