Table 1.
The role of IL-6/JAK2/STAT3 in cancers.
| First author, year | Cancer type | The role of IL-6/JAK2/STAT3 | Model systems |
|---|---|---|---|
| Zhang et al., 2018 | Liver cancer | The levels of IL-6, phosphorylated JAK2 and phosphorylated STAT3 were significantly increased in liver cancer cells (27). | Liver cancer cell lines LO2, hepG2, Huh7, SK‐Hep1, LM3 and MHCC‐97L. Liver cancer tissue samples and paired adjacent normal tissues. NOD/SCID mice model. |
| Shen et al., 2022 | BC | HOXC10 promotes BC tumorigenesis by activating IL-6/JAK2/STAT3 signals (119). | BC tissues and adjacent normal tissues. Human BC cell lines (MCF7, T47D, MDA-MB-453, and MDA-MB-231) and human breast epithelial cells (MCF10A). Male BALB/c nude mice model. |
| Wang et al., 2018 | The cancer promoting effect of P16 is related to the activation of IL-6/JAK2/STAT3 pathway. Inhibition of P16 reduces the growth and metastatic potential of BC cells by inhibiting IL-6/JAK2/STAT3 signal transduction (122). | Human BC cell lines MDA-MB-231, MCF7, and BT-549; human fetal lung fibroblast cell line 2BS; human CRC cells SW-620 and LOVO; human osteosarcoma cell line U-2OS; human prostate cancer cell lines LncaP, DU145, and PC-3; human pancreas cancer cell line PANC-1; human cervical cancer cell line Ca ski; human esophagus cancer cell line TE-1; human esophagus cancer cell line KYSE-510. BC specimens and the corresponding para-carcinoma tissues. BALB/c-nu mice model. | |
| Cheng et al., 2020 | Iron overload can promote EMT of TNBC MDA-MB-231 cells and cell migration by enhancing IL-6/JAK2/STAT3 signaling pathway (50). | Human breast carcinoma cell lines (MDA-MB-231, Hs578T, MCF-7, and T47D) and murine breast carcinoma cell line (4TO7). BALB/c mice model. | |
| Zhu, 2014 | CRC | BMF promotes tumorigenesis by activating IL-6/JAK2/STAT3 pathway (17). | Mouse colon cancer cell line CT26 cells and human colon cancer cell line SW480 cells. BMFs EGFP+ isolated from dysplastic gastric tissues of EGFP + bone marrow-transplanted IL-1β transgenic mice. BALB/c athymic nude mice model. |
| Liu et al., 2022 | GC | RBMS1 activates IL-6 and stimulates downstream JAK2/STAT3 signaling pathway to promote GC metastasis (7). | GC cell lines MGC-803, BGC-823, SGC-7901 and other GC cell lines. GC tissues and paired adjacent noncancerous gastric FFPE tissues. BALB/c nude mice model. In vivo xenograft model. |
| Wu et al., 2017 | CAF in tumor microenvironment promotes GC progression through IL-6/JAK2/STAT3 signal transduction (6). | Plasma samples from GC patients and healthy volunteers. GC tissues from patients. GC cell lines SNU-1, MKN45, SGC7901 and MKN28. BALB/c nu/nu nude mice model. Tumor xenograft model. | |
| Hsu et al., 2012 | Lung cancer | In lung cancer, mesenchymal stem cells can enhance tumorigenesis by activating IL-6/JAK2/STAT3 pathway (22). | Lung cancer cell lines A549 and CL1-5; primary MSCs from different normal human volunteers. NOD/SCID mice model. |
| Lee et al., 2019 | LDOC1 mediates cancer progression through IL-6/JAK2/STAT3 (151). | Human bronchial epithelial cell line BEAS-2B, LADC cell lineA549, NSCLCs cell lines H460, H1299, and H1355. Specimens from human primary NSCLC tumors. BALB/C nu/nu nude mice model. Mouse xenogaft tumor model. | |
| Liu, 2015 | IL-6/JAK2/STAT3 pathway enhances the proliferation of lung CSC by downregulating p53 and p21, caused by DNA hypermethylation, and upregulating DNMT1 (153). | Lung cancer cell lines including A549, CL1-1 and H1650. Tumor xenograft mouse model. | |
| Shi et al., 2017 | TGF-β and IL-6/JAK2/STAT3 pathway form a positive feedback signal loop, mediating the interaction between MFs and lung cancer cells (21). | CMT-167 cells and LLC cells. BMFs isolated from dysplastic gastric tissues of EGFP+ bone marrow-transplanted IL-1β transgenic mice. Tumor tissues from in vivo experiments. BALB/c athymic nude mice model. Tumor xenograft model. | |
| Liu et al., 2015 | PC | The activation of REG3A will enhance JAK2/STAT3 pathway, amplify the carcinogenic effect of IL-6/JAK2/STAT3, and ultimately leads to excessive PC cell proliferation in vitro and in vivo and tumor formation (5). | Human PC cell lines BxPC-3, AsPC-1 and SW1990; cell line HPDE6c7. Tumor tissues. Xenografted mice. |
| Wang et al., 2018 | OC | CAFs highly secrete IL-6 through JAK2/STAT3 pathway and promote β-TGF-mediated EMT, thereby inhibiting apoptosis (18). | Human ovarian cancer cell line OVCAR3. Primary OC cells, CAFs and NFs isolated from fresh cancer tissue. OC tissues. |
| Kim et al., 2017 | ASCs participate in promoting OC cell growth and migration by activating IL-6/JAK2/STAT3 pathway (19). | Human OC cell line SKOV3, ASCs cultured. Human subcutaneous and visceral adipose tissues from patients with benign urologic or gynecologic diseases. |
BC, breast cancer; CRC, colorectal cancer; GC, gastric cancer; PC, pancreatic cancer; OC, ovarian cancer; HCC, hepatocellular carcinoma; HOXC10, homeodomain-containing gene 10; TNBC, triple negative breast cancer; BMF, bone marrow-derived myofibroblasts; CAF, cancer-associated fibroblasts; LDOC1, Leucine Zipper Down-Regulated In Cancer 1; DNMT1, DNA methyltransferase 1; TGF-β, transforming growth factor-β; MFs, myofibroblasts; CSC, cancer stem cell; ASCs, adipose stromal cells; FFPE, formalin-fixed, paraffin-embedded; MSCs, mesenchymal stem cells; LADC, lung adenocarcinoma; NFs, normal fibroblasts; NOD/SCID, non-obese diabetic/severe combined immunodeficiency; SCLC, small cell lung carcinoma; NSCLC, non-SCLC.