Review
Copyright ©The Author(s) 2023.
World J Diabetes. Jul 15, 2023; 14(7): 977-994
Published online Jul 15, 2023. doi: 10.4239/wjd.v14.i7.977
Table 1 Studies published between 2018 and 2022 on receptor for advanced glycation products-ligands, related activated pathways, and cancer hallmarks in the most frequent neoplasms found in diabetic patients
Neoplasia
Ligands and signaling pathway
Molecule expressed
Cancer hallmarks
TS/AM/CL
Ref.
Breast cancerAGE/RAGE, ERK1/2; Akt, c-fosIL-8/CXCR1/2Migration and invasionCL; CAFs, TNBC (MDA-MB-231 cells)Santolla et al[137]
HMGA1Cell proliferation, metastasis, and EMTCL; TNBC (MDA-MB-231 and Hs578)Shah et al[138]
HMGB1/RAGEMotility, migration, invasion, and dysregulation of metabolismTS; human breast cancer, AM; NOD/SCID mice, CL; human breast cancer cells (MCF-7, T-470, BT474, MDA-MB-231, ZR-75-30, BT549) and human fibroblast cells HFL1Chen et al[139]
HMGB1/PI3K/AktPD-L1Cell proliferation, migration, invasion, and T-cell apoptosisCL; human breast cancer cells (MDA-MB-231 P, MDA-MB-231 BM)Amornsupak et al[140]
HMGB1, PI3K/Akt, mTORHIF-1α, VEGFMigration and angiogenesisTS; human breast cancer CL; human breast cancer cells MCF-7He et al[141]
HMGB1/RAGEDownregulation of miR-205Cell growth, invasion, and EMTTS; human breast cancer CL; TNBC (MDA-MB-231, MDA-MB-453, MDA-MB-468) and NTNBC (MCF-7, MCF-10F)Wang et al[142]
HMGB1/RAGE, ERK 1/2, CREB Bone metastasis and neurite outgrowth of nervous system cellsAM; 4T1 mice CL; mouse breast cancer 4T1, primary rat nervous system cells DRG, rat DRG/mouse neuroblastoma hybrid cells F11, immortalized rat DRG neuronal cells 50B11Okui et al[143]
S100A14/RAGE, NF-kBCCL2/CXCL5Migration, invasion, and lung metastasisTS; human breast cancer and paired adjacent breast normal, metastatic lymph node, and non-metastatic lymph node AM; BALB/c, BALB/c, SCID beige, C57BL/6J, CMV-CreC57BL/6J, S200-/- and S100A14-/- PyMT mice CL; human breast cancer cells MCF7, MCF10A, T47D, SKBR3, BT549, MDA-MB-231, MCF10AT, MCFCA1h, MCFCA1α and mouse breast cancer cells 4T1Li et al[144]
S100A7/RAGE, PI3K/Akt, ERK1/2, STAT3IGF-1AngiogenesisCL; human breast cancer cells MCF-7, T47D, and HUVECs cellsMuoio et al[145]
S100A7/RAGE, cPLAPGE2, CD163+Immunosuppression, M2-macrophages, CD4+, CD8+, and T cellsAM; NOD SCID gamma mice CL; human breast cancer cells MDA-MB-231, MDA-MB-468 and mouse mammary cancer cells MVT-1Mishra et al[146]
S100A8/A9-RAGE, FAK, Akt, Hippo-YAKFLNA, CTGF, Cyr61Cell proliferation and migrationCL; HEK293T and TNBC (MDA-MB-23 and BT-549)Rigiracciolo et al[147]
LPS/S100A7/TLR4/RAGEMigration and invasionAM; orthotopic breast cancer C57BL/6 mice model CL; murine mammary cancer cells EO771, MTV-1, murine metastatic mammary cells EO.2, human breast carcinoma cells SUM 159, MDA-MB-231 and MDA-MB-468Wilkie et al[148]
acHMGB1/RAGE, S100A4/RAGE, Gas6/AXLCXCR4, CXCL12, CCL2, CD151 and α3β1-integrinCell proliferation, invasion, intravasation, and EMTAM; murine orthotopic mammary cancer CL; human MSCs, geminin overexpressing breast tumors Gem197, Gem240, Gem256, Gem257 and Gem270 cells, CAFs, and M0- TAMs and M2-TAMsRyan et al[149]
Colorectal cancerS100A16Cancer prognostic markerTS; human colorectal cancerSun et al[150]
HMGB1/RAGEPD-1Cancer prognostic marker TS; human colorectal cancer CL; human colorectal cancer cells SW480, and SW620Huang et al[151]
S100B/RAGE, NF-kBVEGF-AProliferation, migration, and angiogenesisCL; human colon cancer cells HCT116Zheng et al[152]
IGF1R-Ras/RAGE-HMGB1,OncogenesisTS; Human colorectal from diabetic patientsNiu et al[153]
AGEs/RAGE, KLF5MDM upregulation and RB and p53 downregulationCancer initiation and developmentAM; diabetic mouse model and CL; human colon cancer cells HCT116Wang et al[154]
TCTP, HMGB1/RAGE, NF-kBInvasion and metastasisTS; human colorectal AM; tumor xenografts BALB/c nude mice CL; human colon adenocarcinoma cells LoVoHuang et al[155]
S100A9/RAGE/TLR4Arg-1, iNOS, IL-10 and ROSImmune suppression and MDSC chemotaxisTS; human colorectal cancer and normal colon CL; Human colorectal cells LoVo, and MDSCsHuang et al[156]
HMGB1/RAGE, Kras/Yap1Cell proliferationCL; human colorectal cancer cells HCT116 and SW480Qian et al[157]
S100B/RAGE, p38/pAkt/mTORVEGF-R2, iNOS, VEGFCell proliferation, migration, invasion, and angiogenesisCL; human colon adenocarcinoma cells CaCoSeguella et al[158]
HMGB1/RAGE, pERK1/2, pDRP1Cell viability, autophagy, and chemoresistanceTS; human colorectal AM; athymic nude BALBC/c mice CL; human colorectal cells SW480, SW620, and LoVoHuang et al[159]
Hepatocellular carcinomaS100A9-TLR4/RAGE-ROS,NETCell proliferation, invasion, and metastasisTS; HBV+ and HBV-hepatocellular carcinoma AM; BALB/c mice and C57BL/6 mice CL; human liver cells QSG-7701, human hepatocellular carcinoma cells HepG2.2.15, mouse hepatocellular carcinoma cells H22 and HUVEC cellsZhan et al[160]
HMGB1/RAGECell proliferation and tumor differentiationTS; primary hepatocellular carcinomaAndo et al[161]
HMGB1/RAGE, ATG7Cell proliferation, fibrosis, and autophagyTS; mouse hepatocellular carcinoma AM; Atg7, RAGE, HMGB1 transgenic C57BL/6JmouseKhambu et al[128]
HMGB1/RAGE, JNK, OCT4/TGFb1miR-21, CD44Migration and invasionTS; human hepatocellular carcinoma AM; BALB/c nu/nu mice CL; human hepatocellular carcinoma cells HepG2, HCCLM3, Huh7, SMMC7721 and MHCC97HLi et al[162]
S100A4/RAGE, b-cateninOCT4, SOX2, CD44 and Nanog (stem cell-associated genes)Fibrosis and carcinogenesisTS; human hepatocellular carcinoma AM; S100a4-EGFP, S100A4+/+GFP, S100A4-/- transgenic mice. CL; human hepatocellular carcinoma cells Huh7 and murine liver cancer cells Hep1-6Li et al[163]
HMGB1/RAGE, ERK1/2CXCL2, IL-8, TNF, IL-6, IL-10, IL-23-p19Macrophage activation and inflammationAM; primary murine hepatocytes from male C57BI/6J mice, and primary murine splenocytes from male C57BI/CJ CC; murine hepatoma cells Hepa1-6 and Hep-56.1D, human hepatoma cells HepG2, RAW 264.7 macrophages and monocytic cells THP1Bachmann et al[164]
HMGB1/RAGE, NF-kBcircRNA 101368, miR-200aCell migrationTS; human hepatocellular carcinoma CL; human hepatocellular carcinoma cells HCCLM3, MHCC97L, SMMC7721, Hep3B, HepG2 cells, and normal hepatocyte cells THLE-3Li et al[165]
Pancreatic cancerRAGENETNeutrophil autophagyTS; human pancreatic carcinoma AM; Wild type C57BL6 mice and RAGE-/- C57BL6 mice, orthotopic pancreatic cancer model, CL; murine pancreatic cancer cells Panc02, MDSCs cellsBoone et al[166]
RAGE, PI3K/AKT/mTORCell viabilityCL; human pancreatic cancer cells MIA Paca-2, BxPC-3, AsPC-1, HPAC, PANC-1, MIA PacaGEMRLan et al[167]
RAGE, ERK1/2/AktAlpha 2 and alpha 1 integrin downregulationCell proliferation, invasion, and migrationCL; human pancreatic cancer cells Panc-1Swami et al[129]
AGE/RAGE, TGFb1a-SMA, collagen 1, IL-6Fibrosis and EMTTS; human pancreatic ductal adenocarcinoma AM; WT-C57BL/6 and RG-C57BL/6 mice CL; primary PSC, human pancreatic ductal adenocarcinoma cells BxPC-3 and AsPC-1Uchida et al[168]
HMGB1/RAGE, PI3K/AktAtg5, Beclin-1, LC3-IIAutophagia and apoptosis inhibitionCL; human pancreatic cancer cells MIA Paca-2 and MIA PacaGEMRChen et al[169]