Obesity and cancer stem cells: Roles in cancer initiation, progression and therapy resistance

Figure 1 Relative risk of individual cancers at high body mass index. Data were obtained from a meta-analysis reported by the International Agency for Research on Cancer working group. The number represents the relative risk and its 95% confidence interval of the highest body mass index category vs normal body mass index. NA: Not available.

Figure 2 Mechanisms linking obesity and cancer stem cells. In the obese microenvironment, the stem cell pool is increased and loses niche dependence, predisposing these stem cells to transformation. Several main factors are considered to connect obesity and cancer stem cells (CSCs): Components of pro-obesity diets, metabolic and hormonal alterations associated with obesity, dysfunctional adipose tissue in the tumor microenvironment, low-grade obesity-related inflammation, self-renewal and stemness pathways, and microbiome dysbiosis. These factors are intimately linked to and cross-talk with each other, synergistically leading to the activation of CSC programs through various signaling pathways. ASC: Adipose stem cell; BAs: Bile acids; CSC: Cancer stem cell; CTC: Circulating tumor cell; FAs: Fatty acids; FABPs: Fatty acid binding proteins; FAO: Fatty acid oxidation; IGF: Insulin-like factor; IGFR: Insulin-like receptor; LDs: Lipid droplets; LEP: Leptin; LEPR: Leptin receptor; LRP: Low-density lipoprotein receptor-related protein; NCID: Notch intracellular cytoplasmic domain; PI3K: Phosphatidylinositol 3-kinase; PPAR-δ: Peroxisome proliferator-activated receptor δ; TAZ: Transcriptional coactivator with PDZ-binding motif; TFs: Transcription factors; TLR: Toll-like receptor; TNF: Tumor necrosis factor; TNFR: Tumor necrosis factor receptor; YAP: Yes-associated protein; NF-κB: Nuclear factor-kappaB.