Table 1.
Potential roles of CAAs in CRC progression and metastasis.
| Pathways/Key Gene/Molecules/Receptors | Function | References | ||
|---|---|---|---|---|
| Adipokines | Leptin | c-Jun, Akt, and JAK/STAT3 axis IL-6, MMPs, and TGF-β ↑ |
carcinogenesis metastasis |
[5,14] |
| Adiponectin | AMPK axis | inhibition of tumor cell proliferation, angiogenesis, and metastasis |
[5,64,65] | |
| Apelin | tumor growth and migration pathways | lymph node and distant metastasis | [75] | |
| Gherlin | gherlin gene ↓ | increase in TME inflammation | [58] | |
| Resistin | Toll-like receptor 4 ↑ IL-6 and TNF-α ↑ |
promotion of tumor angiogenesis and metastasis | [1,76] | |
| Visfatin | ERK1/2, p38 MAPK, PI3K/mTOR, JNK, and JAK/STAT axis visfatin/SDF-1/Akt axis |
support of tumor cell proliferation and metastasis inhibition of 5-FU therapeutic effect |
[79,80] | |
| Insulin | PI3K/Akt pathway | increase in the resistance to 5-FU and cycloheximide cytotoxicity inhibition of tumor cell proliferation and metastasis |
[81,84] | |
| IFGs | Src (tyrosine-protein kinase) | carcinogenesis proliferation of tumor cells |
[85,86] | |
| VEGF | VEGF gene | tumor angiogenesis and metastasis | [96] | |
| IL-6 | STAT3 axis | support of tumor growth and metastasis | [5,88,89] | |
| TNF-α | NF-kB, Wnt/β-catenin, ERK1/2 axis | carcinogenesis and tumor cell migration | [90,91,92] | |
| PAI-1 | PAI1–tPA axis | increase in TGF-β expression in colitis CRC carcinogenesis and metastasis (?) |
[94] | |
| CCL2 | CCL2 gene | increase in TME macrophages infiltration and induction of tumor progression |
[14] | |
| MMP9 and MMP11 | MMP genes | induction of tumoral extracellular matrix remodeling and metastasis | [1,4,5,28] | |
| Metabolites | Lactate Pyruvate ATP |
fatty acids oxidation | tumor growth and metastasis | [5,28] |
| FFAs | FFAs receptors (FABPs and CD36) | increase in ROS synthesis and fatty acids oxidation promotion of tumor growth and metastasis |
[101,102,103] | |
| Glutamine | CXCL2-VEGFA axis | support of angiogenesis, tumor growth and metastasis | [108,109] | |
| Immune cells activity modulation | IL-6 leptin |
JAK/STAT3 axis | promotion of MDSCs infiltration reduction in NK cells cytotoxicity modulation of the innate and adaptive immune response |
[48,113] |
| FFAs | FFA uptake | induction of neutrophils recruitment | [5,111,112] | |
| FFAs Lactate Glycerin |
metabolic remodeling VEGF |
reduction in T cells antitumoral activity and dendritic cells activation tumor angiogenesis and metastasis |
[5,28,113] | |
| PD-L1 | glycolysis and FAO | reduction in CD4+ and CD8+ T cells activity induction of M2-like macrophages polarization promotion of tumor growth and metastasis |
[5,28] | |
| MAIT-derived IL-17 | IL-23/IL-17 axis | promotion of MDSCs recruitment increase in VEGF and Bcl-2 in TME and Bcl-x expression in tumor cells carcinogenesis and tumor growth |
[110,118] |
ATP—adenosine triphosphate; CAAs—cancer-associated adipocytes; CCL2—chemokine (C-C motif) ligand 2; CRC—colorectal cancer; IFGs—insulin-like growth factors; IL—interleukin; FAO—fatty acid oxidation; FABPs—fatty acid binding proteins; FFAs—free fatty acid; MAIT—mucosal-associated invariant T cell; MDSCs—myeloid-derived suppressor cells; MMP—matrix metalloproteinase; NK cells—natural killer cells; PAI-1—plasminogen activator inhibitor-1; PD-L1—programmed death-ligand 1; ROS—reactive oxygen species; TGF-β—tumor growth factor β; TME—tumor microenvironment; TNF-α—tumor necrosis factor α; VEGF—vascular endothelial growth factor; 5-FU—5-fluorouracil; ↑—increase; ↓—decrease; (?)—working hypothesis.