Table 2.
Transmembrane semaphorins implicated in cancer development.
| Target protein | Functions potentially relevant in cancer |
|---|---|
| Sema4A | Suppresses angiogenesis via PlexinD1158 |
| Germline variant is associated with increased risk for colorectal cancer59 | |
| Sema4B | Interacts with CLCP1,a protein with high sequence similarity to neuropilins and regulates motility of lung cancer cells7 |
| Repressed by HIF-1 α to promote non-small cell lung cancer invasion60 | |
| Inhibits MMP9 to prevent metastasis and inhibits growth invitro and invivo of non-small cell lung cancer61,62 | |
| Sema4C | Elevated expression in esophageal, gastric and rectal carcinomas63 |
| Mutated in some colorectal cancer cell lines159 | |
| Promotes invasive growth in malignant gliomas66 | |
| Regulated by MiR-138 and involved in cell proliferation and epithelial mesenchymal transition in non-small cell lung cancer cells160 | |
| Regulated by MiR-125b and involved in paclitaxel-resistance of breast cancer cells and epithelial to mesenchymal transition in lung cancer64in breast cancer65 | |
| Sema4D | Promotes angiogenesis by stimulating Rho pathways74 |
| Associated with poor clinical outcome in cervical cancer161 | |
| Promotes tumor angiogenesis and progression,as TAMs are a major source of Sema4D13 | |
| Induces angiogenesis by Met recruitment to Plexin B112 | |
| Promotes tumor associated macrophage dependent metastatic behavior in colon cancer162 | |
| Regulated by HIF-1which affects tumor growth and vascularity163 | |
| Increases tumor cell motility via Plexin B1 in pancreatic cancer cells68 | |
| Activates NF-KappaB and IL-8 to promote a pro-angiogenic response in endothelial cells77 | |
| Promotes growth and invasion in HeLa cells164 | |
| Promotes perineural invasion in a RhoA/ROK-dependent manner80 | |
| Overexpression is related to poor prognosis in ovarian cancer165 | |
| Suppresses c-Met activation and migration and promotes melanocyte survival166 | |
| Cooperates with VEGF to promote angiogenesis and tumor progression79 | |
| Over expression as a poor prognosis marker in ovarian cancer and promotes monocyte differentiation toward M2 macrophage167 | |
| Promotes proliferation, migration and invasion in lung cancer cells168 | |
| Recruits pericyte and regulates vascular permeability through endothelial production of PDGF-B and ANGPLT471 | |
| Promotes osteosarcoma development and metastasis72 | |
| Blocking Sema4D with monoclonal anti Sema4D antibody promotes immune infiltration into tumor and enhances response to various other immunomodulatory therapies85 | |
| Induction of expansion of myeloid derived suppressor cells by Sema4D derived from Head and Neck Squamous Cell Carcinoma169 | |
| Sema4F | Biomarker of aggressive prostate cancer and critical regulator of neuroepithelial interactions86,170 |
| Sema4G | Significantly downregulated in colorectal cancer171 |
| Sema5A | Identified as a functional cell adhesion molecule with potential role in metastasis172 |
| Inhibits glioma cell motility through RhoGDIalpha-mediates inactivation of Rac1-GTPase88 | |
| Identified as a novel biomarker for non-small lung carcinoma in non smoking women90 | |
| Promotes angiogenesis by increasing endothelial cell proliferation, migration and decreasing apoptosis173 | |
| Highly expressed in pancreatic cancer and associated with tumor growth, invasion and metastasis174 | |
| Soluble Sema5A suppresses pancreatic tumor burden but increases metastasis and endothelial cell proliferation175 | |
| Sema5B | Promotes cell viability of Clear cell renal carcinoma89 |
| Repressed by FoxP1 in endothelial cells 176 | |
| Sema5C | Required for I(2)gl cancer metastatic phenotype in drosophila model system177 |
| Sema6A | Promotes tumor progression and angiogenesis by enhancing VEGF and bFGF signaling92,,178 |
| Controls cell growth and survival of BRAFV600E human melanoma cells91 | |
| Prognostic biomarker in glioblastoma179 | |
| Sema6B | Expression is downregulated by all-trans-retinoic acid in glioblastoma180 and by PPAR and RXR ligands in breast cancer cells181 |
| Expression is strongly downregulated in breast cancer and a new isoform of Sema6B is identified182 | |
| Sema6D | Activates VEGF-2 and NF-KappaB to mediate survival of malignant mesothelioma cells183 |
| Co-predictor in breast cancer survival184 | |
| Putative driver of osteosarcoma development and metastasis72 |