Table 2.
Functional and mechanistic evidence supporting role of FOXC1 in plasticity, EMT, chemoresistance, cancer progression and metastasis.
| Cancer Type | Transcriptional Addiction | Cell Proliferation | Cellular Plasticity/Stemness | EMT/pEMT/MET | Circulating Tumor Cells (CTCs) | Endocrine Resistance | Chemoresistance | Radioresistance | Cancer Progression/Metastasis | Molecular Pathway | Summary of Findings | Reference |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Breast |
|
|
FOXC1 regulates CD44+ normal mammary progenitors | (61) | ||||||||
| Breast |
|
|
|
|
1st Report of FOXC1 as a marker of aggressive traits | (38) | ||||||
| Breast |
|
FOXC1 is associated with chemoresistance | (62) | |||||||||
| Breast |
|
FOXC1 is associated with radioresistance | (63) | |||||||||
| Breast |
|
|
|
ERα | BRCA1 and GATA3 transcriptionally represses FOXC1 | (64) | ||||||
| Breast |
|
|
TGFβ | Elevated FOXC1 in breast CTCs | (65) | |||||||
| Breast |
|
Transient vs Stable overexpression of FOXC1 | (66) | |||||||||
| Breast |
|
|
NFĸB | NFĸB inhibitor blocks FOXC1 mediated M/I | (67) | |||||||
| Breast |
|
|
Raf/MEK/MAPK | FOXC1 downregulation associated with MET | (68) | |||||||
| Breast |
|
|
|
TGFβ | FOXC1 in breast CTCs associated with progression | (69) | ||||||
| Breast |
|
FOXC1 is enriched in mammary luminal progenitors | (70) | |||||||||
| Breast |
|
|
Ras/ERK, PI3K/AKT | EGFR inhibitor blocks FOXC1 mediated M/I | (71) | |||||||
| Breast |
|
FOXC1 is a marker of neoadjuvant chemoresistance | (72) | |||||||||
| Breast |
|
|
|
FOXCUT | FOXC1-FOXCUT form mRNA-lncRNA pair | (73) | ||||||
| Breast |
|
|
C-Wnt, NFĸB | NFĸB blocks stem cell escape following Wnt inhibition | (74) | |||||||
| Breast |
|
|
|
|
FOXC1/FOXA1 transcriptional balance in breast cancer | (74) | ||||||
| Breast |
|
|
NC-Hedgehog | FOXC1 induces Gli2 activation and NC Hedgehog | (43) | |||||||
| Breast |
|
CDK7 | CDK7-dependent SE-mediated FOXC1 addiction | (75) | ||||||||
| Breast |
|
ERα | FOXC1 transcriptionally represses ERα | (76) | ||||||||
| Breast |
|
FOXC1 overexpression induces increased lung metastasis | (77) | |||||||||
| Breast |
|
ERα | FOXC1 transcriptionally represses ERα | (78) | ||||||||
| Breast |
|
FOXC1 is a marker of adjuvant Anthracycline resistance | (44) | |||||||||
| Breast | EGFR, NFĸB | NFĸB mediates EGF-induced FOXC1 expression | (79) | |||||||||
| Breast |
|
|
TGFβ, FGFR1 | TGFβ upregulates FOXC1, triggers FGFR1 isoform switch | (80) | |||||||
| Breast |
|
FOXC1 inhibits ELF5, lobuloalveolar development | (81) | |||||||||
| Breast |
|
NC-Wnt, NFĸB | FOXC1 mediates Wnt5A-NfĸB-MMP7 induced invasion | (82) | ||||||||
| Breast |
|
Alternative splicing switch in FLNB induces FOXC1, EMT | (83) | |||||||||
| Breast |
|
|
FAK-AKT-mTOR | ST8SIA1 regulates FOXC1 | (84) | |||||||
| Breast |
|
|
CXCR4 | CXCR4-inhibitor blocks FOXC1 mediated M/I, metastasis | (85) | |||||||
| Breast |
|
EZH2 | EZH2 epigenetically represses FOXC1 | (86) | ||||||||
| Breast | FOXC1 upregulates LINC01123, ↓miR663a | (49) | ||||||||||
| Breast |
|
|
|
|
CDK7 | FOXC1 contributes to CDK7-inhibitor sensitivity | (87) | |||||
| Breast |
|
|
|
FOXC1 is most significant EMAT/metastasis activator | (88) | |||||||
| Breast |
|
|
|
CDK7 | FOXC1 is most significant invasion/metastasis activator | (89) | ||||||
| Prostate |
|
|
FOXC1 expression associated with AIPC progression | (90) | ||||||||
| Prostate |
|
EGFR | EGFR upregulates FOXC1 | (91) | ||||||||
| Prostate |
|
|
|
MiR-138-5P inhibits FOXC1-mediated M/I | (92) | |||||||
| Prostate |
|
|
|
MiR-138-5P inhibits FOXC1-mediated M/I | (49) | |||||||
| Lung |
|
|
|
FOXC1 drives proliferation, EMT, invasion | (93) | |||||||
| Lung |
|
|
|
HIF1α | HIF1α transcriptionally upregulates FOXC1 | (94) | ||||||
| Lung |
|
|
β-catenin, C-Wnt | FOXC1 transcriptionally upregulates β-catenin | (56) | |||||||
| Lung |
|
|
lncRNA CCAT2 upregulates FOXC1 | (95) | ||||||||
| Lung |
|
|
LOX | FOXC1 transcriptionally upregulates LOX, ↑metastasis | (57) | |||||||
| Lung |
|
|
HIF1α | FOXC1 transcriptionally upregulates LINC00301, ↑HIF1α | (96) | |||||||
| Cervical |
|
|
PI3K/AKT | FOXC1 mediates PI3K/AKT induced EMT, M/I | (45) | |||||||
| Cervical |
|
|
miR-374c-5p inhibits FOXC1-mediated M/I | (45) | ||||||||
| Cervical |
|
|
FOXC1 is associated with radioresistance | (29) | ||||||||
| Cervical |
|
PI3K/AKT | FOXC1 mediates PI3K/AKT induced M/I | (46) | ||||||||
| Endometrial |
|
|
miR-204 inhibits FOXC1-mediated proliferation, M/I | (97) | ||||||||
| Endometrial |
|
|
miR-495 inhibits FOXC1-mediated proliferation, M/I | (98) | ||||||||
| Esophageal |
|
FOXCUT | FOXC1-FOXCUT form mRNA-lncRNA pair | (50) | ||||||||
| Esophageal |
|
|
|
FOXC1 acts as transcriptional coactivator of, PBX1, ↑ZEB2 | (51) | |||||||
| Gastric |
|
β-catenin, C-Wnt | FOXC1 transcriptionally downregulates DKK1, activating Wnt | (53) | ||||||||
| Gastric |
|
|
Wnt | FOXC1 transcriptionally upregulates GPX8, activating Wnt | (99) | |||||||
| Gastric |
|
|
|
LINC00242 inhibits miR-141, upregulates FOXC1 | (100) | |||||||
| Gastric |
|
|
|
MCM3AP-AS1 inhibits miR-148, upregulates FOXC1 | (101) | |||||||
| Gastric | EGFR | EGFR-FOXC1 upregulates histone H3C14 | (102) | |||||||||
| Pancreatic |
|
|
|
miR-138-5p inhibits FOXC1,↓ proliferation,↓ tumor growth | (103) | |||||||
| Pancreatic |
|
|
|
|
PI3K/AKT/mTOR | FOXC1 and IGF1R positively regulate each other | (104) | |||||
| Hepatic |
|
|
|
|
VEGF | FOXC1 | (105) | |||||
| Hepatic |
|
|
|
NEDD9 | FOXC1 transcriptionally upregulates NEDD9, ↑metastasis | (54 | ||||||
| Hepatic |
|
IL8,PI3K/AKT,CXCR1 | IL8-dependent PI3K/AKT/HIF1α upregulates FOXC1 | (106) | ||||||||
| Hepatic |
|
HOTAIR | FOXC1 upregulates lncRNA HOTAIR, ↓miRNA-1 | (107) | ||||||||
| Colon |
|
FGFR4 | FOXC1 transcriptionally upregulates ITGA7, FGFR4 | (47) | ||||||||
| Colon |
|
|
FOXC1 transcriptionally upregulates FBP1, ↑Warburg Effect | (48) | ||||||||
| Colon |
|
FOXC1 transcriptionally upregulates miR-31-5p, ↓LATS2 | (108) | |||||||||
| Colon |
|
|
p38MAPK maintain FOXC1 protein stability, ↑metastasis | (49) | ||||||||
| Colon |
|
> | FOXC1 induces resistance to oxaliplatin, irinotecan | (109) | ||||||||
| OSCC |
|
|
FOXCUT | FOXC1-FOXCUT form mRNA-lncRNA pair | (110) | |||||||
| OSCC |
|
|
|
FOXC1 transcriptionally upregulates CCNB1/D1, MMP2/9 | (47) | |||||||
| OSCC |
|
|
|
MCM3AP-AS1 inhibits miR-138, upregulates FOXC1 | (111) | |||||||
| Tongue |
|
|
|
TGFβ | miR-639 inhibits FOXC1-mediated EMT, M/I | (60) | ||||||
| SACC |
|
|
|
|
miR-582-5p inhibits FOXC1, ↓M/I, ↓metastasis | (78) | ||||||
| LSCC |
|
miR-204-5P inhibits FOXC1-mediated M/I | (112) | |||||||||
| NP |
|
FOXC1 associated with low E-cadherin expression | (113) | |||||||||
| NP |
|
|
|
FOXC1 siRNA inhibited EMT, M/I | (114) | |||||||
| NP |
|
|
|
miR-4792 inhibits FOXC1-mediated EMT, M/I | (115) | |||||||
| NP |
|
|
FOXCUT | FOXCUT siRNA inhibited FOXC1-mediated MMP7/9 | (44) | |||||||
| OS |
|
|
|
miR-133b inhibits FOXC1-mediated proliferation, M/I | (116) | |||||||
| OS |
|
|
|
EZH2 | FOXC1 transcriptionally upregulates EZH2 | (117) | ||||||
| OS |
|
|
β-catenin, C-Wnt | Sp1/FOXC1/HOTTIP/LATS2/YAP/β-catenin cascade | (118) | |||||||
| OS |
|
|
|
miR-185-5p inhibits FOXC1-mediated M/I | (119) | |||||||
| Melanoma |
|
|
PI3K/AKT | FOXC1 mediates MST1R mediated colony formation, M/I | (120) | |||||||
| WT |
|
|
|
HOXB2 and FOXC1 synergistically drive progression | (121) | |||||||
| GB |
|
|
miR-133 inhibits FOXC1-mediated M/I | (47) | ||||||||
| GB |
|
|
|
β-catenin, C-Wnt | FOXC1 siRNA inhibited EMT, M/I | (122) | ||||||
| Pituitary |
|
miR-133 inhibits FOXC1, ↓M/I | (120) | |||||||||
| AML |
|
|
|
FOXC1, HOXA9 ↑clonogenic potential, ↓differentiation | (39) | |||||||
| T-ALL |
|
NC-Hedgehog | FOXC1 stabilizes GLI2, drives SMO-inhibitor resistance | (123) | ||||||||
| HL |
|
|
FGF2 | OTX2 transcriptionally activates FOXC1 | (124) | |||||||
| DLBCL |
|
|
JUN upregulates FOXC1, drives lymphoma dissemination | (125) |
AIPC, Androgen Insensitive Prostate Cancer; AML, Acute Myelogenous Leukemia; C-, Canonical; CTC, Circulating Tumor Cells; DLBCL, Diffuse Large B Cell Lymphoma; EMT, Epithelial-to-mesenchymal; GB, Glioblastoma; HL, Hodgkins Lymphoma; LSCC, Laryngeal Squamous Cell Carcinoma; MET, Mesenchymal-to-epithelial; NC-, Non-canonical; NP, Nasopharyngeal Carcinoma; OS, Osteosarcoma; OSCC, Oral Squamous Cell Carcinoma; pEMT, Partial Epithelial-to-mesenchymal; SACC, Salivary Squamous Cell Carcinoma; T-ALL, T Cell Acute Lymphocytic Leukemia; WT, Wilms tumor.