Table 3.
Possible mechanisms of leptin-induced cancer cell proliferation
| Investigators and Cancer types | Involved intracellular signaling pathways/Mechanisms | Principal mediating factors/phenomena |
|---|---|---|
| Blanquer-Rosselló Mdel et al. 2016 [167] MCF-7 breast cancer cells |
Lipid metabolism pathways, AMPK | Leptin favored the use of glucose for biosynthesis and lipids for energy production |
| Chen et al. 2013 [168] OVCAR-3 ovarian cancer cells |
PI3K/AKT and MEK/ERK1/2 pathways | Leptin enhanced the expression of regulators of cell proliferation and apoptosis inhibition, cyclin D1 and Mcl-1 |
| Chin et al. 2017 [169] SKOV-3 and OVCAR-3 ovarian cancer cells |
PI3K, STAT3, ERK1/2 | Leptin increased FSH, stimulated ERα and the expression of ERα-responsive genes |
| Dubois et al. 2014 [170] MCF-7 and T47D breast cancer cells |
Estrogenic pathway, leptin autocrine/paracrine signaling loop | Leptin stimulated proliferation, overexpression of leptin, Ob-R, ER, and aromatase |
| Habib et al. 2015 [171] PC-3 prostate cancer cells |
Estrogenic pathway | Leptin increased the expression of ERα, aromatase and CYP1B1, and decreased the expression of ERβ and COMT |
| Harbuzariu et al. 2017 [172] BxPC-3, MiaPaCa-2, Panc-1, AsPC-1 pancreatic cancer cells |
Notch signaling pathway, leptin autocrine/paracrine signaling loop | Leptin increased cell cycle progression and proliferation |
| Kim et al. 2017 [173] MCF-7 breast cancer cells |
STAT3, AKT, ERK, JNK, PKA, cAMP | Leptin increased COX-2 expression and PGE2 production, increased aromatase expression |
| Liu et al. 2013 [174] Ishikawa endometrial cancer cells |
Estrogenic pathway | Leptin stimulated cell proliferation via enhancing aromatase expression and estradiol synthesis |
| Nepal et al. 2015 [175] HepG2 hepatoma and MCF-7 breast cancer cells |
p53/FoxO3A axis | Leptin augmented the expression of autophagy-related genes, including beclin-1, Atg5 and LC3 II, which caused increase in cell number and suppression of apoptosis |
| Ptak et al. 2013 [176] OVCAR-3 ovarian cancer cells |
Increase in cyclin D1, cyclin A2, and a decrease in p21WAF1/CIP1, Bad, TNFR1, and caspase 6 | Leptin promoted cell proliferation and downregulated apoptotic pathway |
| Qian et al. 2015 [177] MCF-7 and tamoxifen-resistant cells |
ERK1/2, STAT3 | Leptin enhanced proliferation, and CCND1 (cyclin D1) gene transcription by inducing the binding of ERα to the promoter of CCND1 gene |
| Shouman et al. 2016 [178] MCF-7 breast cancer cells |
Estrogenic pathway | Leptin increased CYP1B1 expression and DNA adducts, and diminished COMT protein expression |
| Wang et al. 2012 [116] HCT-116 colon cancer cells |
PI3K/AKT/mTOR pathway | Leptin stimulated proliferation and inhibited apoptosis |
| Xu et al. 2013 [179] SKOV3 and A2780 ovarian cancer cells |
STAT5 | Leptin promoted cell proliferation in cooperation with microRNA-182 and microRNA-96 (targeting FoxO3) |
| Yoon et al. 2014 [180] LS174T, HCT-116 and CaCo-2 colon cancer cells |
JAK and ERK signaling pathways | Leptin increased the number of cells |
AKT: v-Akt murine thymoma viral oncogene or protein kinase B (a serine/threonine kinase), AMPK: AMP-activated protein kinase, Atg5: autophagy protein 5, cAMP: cyclic AMP, COMT: catechol-o-methyltransferase, COX-2: cyclooxygenase-2, CYP1B1: cytochrome P450 1B1, ER: estrogen receptor, ERK: extracellular signal-regulated kinase, FoxO3A: forkhead box O3, FSH: follicle-stimulating hormone, JAK: Janus kinase, JNK: c-Jun N-terminal kinase, LC3: light chain 3 (microtubule-associated), Mcl-1: myeloid cell leukemia 1, MEK: mitogen-activated protein kinase kinase, mTOR: mechanistic/mammalian target of rapamycin, Ob-R: leptin receptor, p21WAF1/CIP1: cyclin-dependent kinase inhibitor, PGE2: prostaglandin E2, PI3K: phosphatidylinositol-3-kinase, PKA: protein kinase A, STAT3: signal transducer and activator of transcription 3, TNFR1: tumor necrosis factor receptor 1