Limits...
c-MYC responds to glucose deprivation in a cell-type-dependent manner

View Article: PubMed Central - PubMed

ABSTRACT

Metabolic reprogramming supports cancer cells’ demands for rapid proliferation and growth. Previous work shows that oncogenes, such as MYC, hypoxia-inducible factor 1 (HIF1), have a central role in driving metabolic reprogramming. A lot of metabolic enzymes, which are deregulated in most cancer cells, are the targets of these oncogenes. However, whether metabolic change affects these oncogenes is still unclear. Here we show that glucose deprivation (GD) affects c-MYC protein levels in a cell-type-dependent manner regardless of P53 mutation status. GD dephosphorylates and then decreases c-MYC protein stability through PI3K signaling pathway in HeLa cells, but not in MDA-MB-231 cells. Role of c-MYC in sensitivity of GD also varies with cell types. c-MYC-mediated glutamine metabolism partially improves the sensitivity of GD in MDA-MB-231 cells. Our results reveal that the heterogeneity of cancer cells in response to metabolic stress should be considered in metabolic therapy for cancer.

No MeSH data available.


Related in: MedlinePlus

c-MYC-mediated glutamine metabolism is involved in the resistance to GD in MDA-MB-231 cells. (a) HeLa and MDA-MB-231 cells were maintained under the indicated medium for different intervals. Cell viabilities were examined by MTT assay. (b) HeLa stable cells expressing MYC were maintained under GD condition for different intervals and cell viabilities were examined by MTT. (c) MDA-MB-231 stable cells expressing c-MYC(ΔN) were treated as in b. (d) GLS1-3′-UTR was transfected into HeLa or MDA-MB-231 cells and maintained under the indicated medium for 36 h. Luciferase activities were examined. *P<0.05, **P<0.01. (e and f) Western blot detection of GLS1 and c-MYC in HeLa (e) and MDA-MB-231 (f) cells under GD condition for different intervals. (g) MDA-MB-231 cells were treated with CB-839 (10 μM) under GD condition for different intervals and cell viabilities were examined by MTT. (h) MDA-MB-231 stable cells infected with lenti-shGLS1 were treated as in (b). (Right) Examination of GLS1 knockdown efficiency by quantitative RT-PCR. Values are normalized to 18S and relative to control group. MTT in (a–c, g and h) were repeated three times, and values are shown as fold changes versus 0 h group.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4979460&req=5

fig6: c-MYC-mediated glutamine metabolism is involved in the resistance to GD in MDA-MB-231 cells. (a) HeLa and MDA-MB-231 cells were maintained under the indicated medium for different intervals. Cell viabilities were examined by MTT assay. (b) HeLa stable cells expressing MYC were maintained under GD condition for different intervals and cell viabilities were examined by MTT. (c) MDA-MB-231 stable cells expressing c-MYC(ΔN) were treated as in b. (d) GLS1-3′-UTR was transfected into HeLa or MDA-MB-231 cells and maintained under the indicated medium for 36 h. Luciferase activities were examined. *P<0.05, **P<0.01. (e and f) Western blot detection of GLS1 and c-MYC in HeLa (e) and MDA-MB-231 (f) cells under GD condition for different intervals. (g) MDA-MB-231 cells were treated with CB-839 (10 μM) under GD condition for different intervals and cell viabilities were examined by MTT. (h) MDA-MB-231 stable cells infected with lenti-shGLS1 were treated as in (b). (Right) Examination of GLS1 knockdown efficiency by quantitative RT-PCR. Values are normalized to 18S and relative to control group. MTT in (a–c, g and h) were repeated three times, and values are shown as fold changes versus 0 h group.

Mentions: c-MYC has been reported to affect cell viability under GD condition60,61 and this effect might vary with cell type.62 We found that HeLa and MDA-MB-231 cells showed distinct response to glucose or glutamine deprivation (Figure 6a). Overexpression of c-MYC in HeLa cells increased cell viability in normal medium, but had negligible effect on cell viability under GD condition (Figure 6b). By contrast, overexpression of a transactivation domain-deleted mutant MYC(ΔN)63 markedly sensitized MDA-MB-231 cells to GD (Figure 6c). These findings suggest that c-MYC might exert different role in HeLa and MDA-MB-231 cells under GD condition.


c-MYC responds to glucose deprivation in a cell-type-dependent manner
c-MYC-mediated glutamine metabolism is involved in the resistance to GD in MDA-MB-231 cells. (a) HeLa and MDA-MB-231 cells were maintained under the indicated medium for different intervals. Cell viabilities were examined by MTT assay. (b) HeLa stable cells expressing MYC were maintained under GD condition for different intervals and cell viabilities were examined by MTT. (c) MDA-MB-231 stable cells expressing c-MYC(ΔN) were treated as in b. (d) GLS1-3′-UTR was transfected into HeLa or MDA-MB-231 cells and maintained under the indicated medium for 36 h. Luciferase activities were examined. *P<0.05, **P<0.01. (e and f) Western blot detection of GLS1 and c-MYC in HeLa (e) and MDA-MB-231 (f) cells under GD condition for different intervals. (g) MDA-MB-231 cells were treated with CB-839 (10 μM) under GD condition for different intervals and cell viabilities were examined by MTT. (h) MDA-MB-231 stable cells infected with lenti-shGLS1 were treated as in (b). (Right) Examination of GLS1 knockdown efficiency by quantitative RT-PCR. Values are normalized to 18S and relative to control group. MTT in (a–c, g and h) were repeated three times, and values are shown as fold changes versus 0 h group.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4979460&req=5

fig6: c-MYC-mediated glutamine metabolism is involved in the resistance to GD in MDA-MB-231 cells. (a) HeLa and MDA-MB-231 cells were maintained under the indicated medium for different intervals. Cell viabilities were examined by MTT assay. (b) HeLa stable cells expressing MYC were maintained under GD condition for different intervals and cell viabilities were examined by MTT. (c) MDA-MB-231 stable cells expressing c-MYC(ΔN) were treated as in b. (d) GLS1-3′-UTR was transfected into HeLa or MDA-MB-231 cells and maintained under the indicated medium for 36 h. Luciferase activities were examined. *P<0.05, **P<0.01. (e and f) Western blot detection of GLS1 and c-MYC in HeLa (e) and MDA-MB-231 (f) cells under GD condition for different intervals. (g) MDA-MB-231 cells were treated with CB-839 (10 μM) under GD condition for different intervals and cell viabilities were examined by MTT. (h) MDA-MB-231 stable cells infected with lenti-shGLS1 were treated as in (b). (Right) Examination of GLS1 knockdown efficiency by quantitative RT-PCR. Values are normalized to 18S and relative to control group. MTT in (a–c, g and h) were repeated three times, and values are shown as fold changes versus 0 h group.
Mentions: c-MYC has been reported to affect cell viability under GD condition60,61 and this effect might vary with cell type.62 We found that HeLa and MDA-MB-231 cells showed distinct response to glucose or glutamine deprivation (Figure 6a). Overexpression of c-MYC in HeLa cells increased cell viability in normal medium, but had negligible effect on cell viability under GD condition (Figure 6b). By contrast, overexpression of a transactivation domain-deleted mutant MYC(ΔN)63 markedly sensitized MDA-MB-231 cells to GD (Figure 6c). These findings suggest that c-MYC might exert different role in HeLa and MDA-MB-231 cells under GD condition.

View Article: PubMed Central - PubMed

ABSTRACT

Metabolic reprogramming supports cancer cells&rsquo; demands for rapid proliferation and growth. Previous work shows that oncogenes, such as MYC, hypoxia-inducible factor 1 (HIF1), have a central role in driving metabolic reprogramming. A lot of metabolic enzymes, which are deregulated in most cancer cells, are the targets of these oncogenes. However, whether metabolic change affects these oncogenes is still unclear. Here we show that glucose deprivation (GD) affects c-MYC protein levels in a cell-type-dependent manner regardless of P53 mutation status. GD dephosphorylates and then decreases c-MYC protein stability through PI3K signaling pathway in HeLa cells, but not in MDA-MB-231 cells. Role of c-MYC in sensitivity of GD also varies with cell types. c-MYC-mediated glutamine metabolism partially improves the sensitivity of GD in MDA-MB-231 cells. Our results reveal that the heterogeneity of cancer cells in response to metabolic stress should be considered in metabolic therapy for cancer.

No MeSH data available.


Related in: MedlinePlus