Table 2.

Highlights of recent publications in relation to methionine restriction outcome and SIRT1/PGC-1α/PPAR-α players in the stemness of cancer stem cells.

Cancer Stem Cells
Cell Type	Experimental Condition	Observed Changes		Reference
		Increased	Decreased
Triple-negative breast CSCs	Met restriction	MAT2A Sensitivity to MAT2A inhibition	Mammosphere formation CD44(hi)/C24(low) CSC population Sox9 expression H3K4me3 mark	[5]
Lung CSCs	Met restriction		SAM levels H3K4me3 and other histone marks Colony-forming abilities in vitro Tumorigenic potential in vivo Cell-surface expression of CD166	[4]
Glioblastoma CSCs	Standard limiting dilution of Met	Mitochondrial SHMT2 and ALDH1L2 SOX2, OCT4, NANOG	Cytoplasmic SHMT1, MTHFD1 and DHFR	[3]
Breast CSCs	Inhibition of OGT (potential relation to methionine cycle)		Mammosphere formation CD44(hi)/C24(low) CSC population NANOG+ population ALDH+ population c-Myc+ population	[9]
Colorectal carcinoma CSCs	SIRT1 knockdown/inhibition		Stemness-associated genes (including Oct4, Nanog, Cripto, Tert and Lin28) Abilities of colony and sphere formation Percentage of CD133+ cells Tumorigenicity in vivo	[58]
Liver CSCs	SIRT1 knockdown/inhibition		Cell growth of liver CSCs Sphere and clone formation efficiencies in vitro Tumorigenic potential in vivo SOX2, Nanog and Oct4 expression levels	[54]
	Overexpression of exogenous SIRT1	Self-renewal of liver non-CSCs Clone and sphere formation efficiencies Tumorigenic potential in vivo
Glioma CSCs	PPARα KD	Astrocytic differentiation	Tumorigenicity of in vivo Proliferative capacity and clonogenic potential in vitro Tumorigenicity of orthotopic xenografts Stem cell markers (SOX2, c-Myc and nestin)	[59]
Liver CSCs	SIRT1 inhibition	Susceptibility to chemotherapeutic drugs Senescence via activation of p53-p21 and p16 pathway	Stemness-associated genes (including NANOG, SOX2, OCT4, CD13, CD44 and EpCAM) Spheroid formation Tumorigenicity in vivo	[52]
Breast CSCs	PPARα agonist	Mammosphere formation NF-κB/IL6 axis Mammosphere regulatory genes		[62]