Table 3.
Contribution of HOX genes in cancer invasion and metastasis
| Cancer | Deregulated HOX genes | Signaling pathway | Targets | Role | References |
|---|---|---|---|---|---|
| Gastric cancer | ↑ HOXC10 | ↑ NF-κB | ATM | Promotes cell migration and invasion; significantly associated with TNM stage, lymph node metastasis, and distant metastasis | Yao et al. 2018 |
| Cutaneous squamous cell carcinoma | ↑ HOXB7 | ↑ Wnt/β-catenin | CTNNB1 | Enhances cell viability, migration, invasion, and metastasis and inhibits apoptosis | Gao and Chen 2018 |
| Osteosarcoma | ↑ HOXB8 | ↑ Wnt/β-catenin | CTNNB1, c-Myc, CCND1 | Promotes proliferation, migration, invasion, and metastasis | Guo et al. 2019 |
| Breast cancer | ↑ HOXB7 | ↑ TGF-β | TGFβ2 | Induces metastasis via TAM recruitment; promotes tumor progression in a cell-autonomous and non-cell-autonomous manner; and enhances migration and invasion | Liu et al. 2015 |
| ↑ HOXC10 | ↑NF-κB | - | Significantly correlated with distant metastasis after chemotherapy | Sadik et al. 2016 | |
| Hepatocellular carcinoma | ↑ HOXB5 | ↑ TGF-β-induced PI3K/AKT | - | Promotes cell migration and metastasis | (Sun et al. 2018) |
| Lung adenocarcinoma | ↑ HOXB7 | ↑TGF-β/SMAD3 | VEGFA, MMP2, SMAD3 | Significantly associated with lymph node metastasis | Zhuang et al. 2015 |
| Prostate cancer | ↑ HOXA1 | ↑ERK1/2 and AKT | ERK1/2, AKT | Promotes cell proliferation, invasion, and metastasis | Wang et al. 2015 |
| ↓ HOXD13 | ↑ TGF-β/BMP4/SMAD1 | SMAD1 | Promotes EMT and metastasis | Xu et al. 2021 | |
| Lung cancer | ↓ HOXA4 | ↑ Wnt/β-catenin | GSK3β; β-catenin, cyclin D1, c-Myc, and survivin | Promotes proliferation, migration, invasion, and lymph node metastasis and inhibits cell cycle arrest | Cheng et al. 2018 |
NOTE: TAM, tumor-associated macrophage; ATM, ataxia telangiectasia mutated; ↑, upregulated; ↓, downregulated