Table 1.
A summary of FOXC1 alterations in cancer, associated clinical outcomes, and functional consequences of experimental manipulation of FOXC1 expression.
| Cancer Type | FOXC1 Alteration | Associated Clinical Outcome | Case Sizes | Functional Impact of Experimental FOXC1 Manipulation | |
|---|---|---|---|---|---|
| Overexpression | Silencing | ||||
| AML | Overexpression | Inferior OS [40,41]; increased risk of relapse and resistance to induction chemotherapy [41] | 270 [40] 765 [41] |
Co-operates in vivo with Hoxa9 to block differentiation and accelerate onset of AML [40] | Loss of clonogenic potential and enhanced morphological differentiation in vitro [40] |
| Breast (BLBC and Luminal B) | Overexpression | BLBC: Increased metastasis; inferior OS [42] | 2073 | BLBC: Increased cell growth/survival [42], induced progenitor-like phenotype in vitro [35]; enhanced CSC-like properties in vitro and in vivo [44]. | BLBC: Impaired cell proliferation, migration and invasion in vitro [42]. |
| Luminal B: improved RFS [43] | 1142 | Luminal B: impaired invasion and lung metastasis formation [43]. | - | ||
| Colorectal | Overexpression | Increased risk of metastasis; inferior OS/RFS [45,46] | 361 [45] 120 [46] |
Increased tumorigenicity and metastasis in vivo [45,46]; enhanced Warburg effect in vitro [45]. | Impaired tumorigenicity and metastasis in vivo [45,46]; inhibited Warburg effect in vitro [45]. |
| Cervical | Overexpression | Increased risk of invasion, metastasis and relapse; inferior OS [47] | 336 | - | Suppressed cell growth, migration and invasion in vitro [48]. |
| Endometrial | Overexpression | - | 20 | Enhanced migration and colony formation in vitro [49,50]. | Increased apoptosis in vitro, impaired tumor growth in vivo [49]. |
| Gastric | Overexpression | Inferior OS/RFS [51] | 120 | - | - |
| Head and Neck (LSCC and NPC) | Overexpression | LSCC: increased risk of lymph node metastasis [52] | 147 | - | - |
| NPC: increased risk of metastasis [53] | 93 | - | - | ||
| Liver (HCC) | Overexpression | Inferior OS; increased relapse risk [54] | 406 | Increased cell invasion in vitro and metastasis in vivo [54]. | Impaired cell invasion in vitro and metastasis in vivo [54]. |
| Lung (NSCLC) | Overexpression | Inferior OS/RFS [55,56] | 125 [55] 1129 [56] |
Enhanced CSC-like properties, drug resistance and tumorigenicity in vivo [56]. | Suppressed self-renewal and impaired tumorigenicity in vivo [56]. |
| Lymphoma (DLBCL and HL) | Overexpression | DLBCL: trend towards increased extranodal spread [57] | 25 | - | - |
| HL: part of Hodgkin Reed-Sternberg cell-specific gene signature correlated with treatment failure [58] | 29 | - | - | ||
| Melanoma | Overexpression | Inferior OS; increased risk of metastasis [59] | 228 | Enhanced cell proliferation and invasion in vitro [59] | - |
| Pancreatic (PDA) | Overexpression | Increased risk of lymph node metastasis, inferior OS [60] | 30 | Increased cell proliferation and invasion in vitro; promoted tumorigenicity in vivo [61] | Impaired cell proliferation and invasion in vitro [61] |
| Esophageal (ESCC) | Overexpression | ESCC: increased rate of metastasis, inferior OS [62]; | 84 | ESCC: promoted ESCC cell proliferation, colony formation and invasion in vitro [63] | ESCC: impaired ESCC cell colony formation, and invasion in vitro [62,63] |
| Osteosarcoma | Overexpression | Higher TNM staging [64] | 42 | - | Impaired cell proliferation and migration in vitro [64] |
| Ovarian (Serous) | Overexpression | Improved OS [65] | 80 | - | - |
AML, acute myeloid leukemia; BLBC, basal-like breast cancer; DLBCL, diffuse large B cell lymphoma; ESCC, esophageal squamous cell carcinoma; HCC, hepatocellular carcinoma; HL, Hodgkin lymphoma; LSCC, laryngeal squamous cell carcinoma; NPC, nasopharyngeal carcinoma; NSCLC, non-small cell lung cancer; OS, overall survival; OSCC, oral squamous cell carcinoma; PDA, pancreatic ductal adenocarcinoma; RFS, relapse-free survival; TNM, tumor-node metastasis; –, data either inconclusive or unavailable.