Table 1.
Transcriptional targets of Hedgehog signaling
| Hedgehog signaling target genes | |
|---|---|
| Cell proliferation and survival | CCND1 (cyclin D1)a |
| BMI‐1 (BMI1 polycomb ringer finger oncogene) | |
| P63 | |
| FOXM1 (forkhead box M1)a | |
| BCL‐2 (B‐cell CLL/Lymphoma 2)a | |
| EMT | SNAI1 (snail family zinc finger 1) |
| FOXM1Mechanism: FOXM1‐mediated upregulation of EMT transcription factor Slug by FOXM1 reported in TNBC | |
| FOXC2a (forkhead box C2 (MFH‐1, mesenchyme forkhead 1)Mechanism not well understood in TNBC. Downregulation of the E‐cadherin stabilizing protein p‐120 catenin by FOXC2 has been described in non‐small‐cell lung cancer | |
| Invasion, migration, angiogenesis | VEGF (vascular endothelial growth factor A) |
| NRP2 (neuropilin 2) | |
| CYR61 (cysteine‐rich, angiogenic inducer, 61) | |
| MMP (matrix metalloproteinase) 2, MMP 9, MMP 11 | |
| FOXM1 via regulating the expression of extracellular matrix degrading factors uPA (urokinase plasminogen activator), uPAR (urokinase plasminogen activator receptor), MMP2, MMP 9 along with VEGF | |
| CXCR4 (chemokine receptor 4) | |
| Osteolytic metastases | PTH‐rP (parathyroid hormone‐like hormone) |
| OPN (SSP1, secreted phosphoprotein 1) | |
| Chemotherapy resistance | ABCB1 (ATP‐binding cassette, subfamily B, member 1) |
| ABCG2 (ATP‐binding cassette, subfamily G, member 2)Anthracycline and taxane resistance.Mechanism: active drug efflux | |
| FOXM1:Anthracycline and cisplatin resistance. Mechanism: induction of double‐stranded DNA repair gene expressionTaxane resistanceMechanism: upregulation of the protein stathmin leading to microtubule disruption and interfering with paclitaxel microtubule binding | |
| BMI‐1Resistance to five fluorouracil (5‐FU)Mechanism: BMI‐mediated inhibition of mitochondrial apoptotic pathways induced by 5‐FU |
a
Established transcriptional targets in non‐mammary cells/tumors.
FOXC2 is the target Hh signaling and other developmental pathways.