Table 2. Experimental evidence for IRAK1 involvement in solid tumor malignancies.
| Tumor Type | Experimental System | Effector(s) | Effects |
|---|---|---|---|
| Breast [82] | MDA-MB-231 cells | MiRNA-146a | MiRNA-146a transfection into BC cells downregulated IRAK1/TRAF6, reduced NF-κB target gene expression, impaired invasion and migration. |
| Breast [147] | TNBC cell lines; MB436 xenograft mouse | IRAK1 shRNA; IRAK1/4 inhibitor I | IRAK1 knockdown or inhibition reduced TNBC cell invasion, mammosphere formation; IRAK1 shRNA inhibits tumor growth in a TNBC mouse model; paclitaxel-treated TNBC cells acquire resistance that can be overcome by IRAK1/4 inhibitor + paclitaxel. |
| Breast [38] | Pt-derived tumorspheres; 1q21.3-amplified HCC70 xenograft mouse; other xenograft models | Pacritinib | Chromosome 1q21.3, encoding IRAK1, is amplified in recurrent BC; S100A7/8/9 and IRAK1 drive tumorsphere growth, disrupted by pacritinib via IRAK1, not JAK2; pacritinib TGI in xenograft models via IRAK1; pacritinib + paclitaxel caused durable tumor regressions in a neoadjuvant TNBC model. |
| Endometrial [148] | Pt tumor tissue; HEC-1B, JEC cells; BALB/c nude mouse | IRAK1 siRNA | IRAK1 tumor levels correlate with survival, stage, metastasis, invasion; knockdown in cells antiproliferative via cell cycle arrest, apoptosis; IRAK1 siRNA transducted cells less tumorigenic in mice. |
| HCC [151] | Pt FFPE liver tissue | NA | IRAK1 expression frequency increased in HCC progression, correlates with tumor size and metastasis; IRAK1 upregulation significantly predicts poor survival. |
| HCC [152] | Pt HCC tissue, HCC cell lines; SMMU-7721 xenograft mouse | IRAK1/4 inhibitor I; IRAK1 siRNA | IRAK1 overexpressed in HCC tissue; IRAK1 siRNA inhibits growth, augments cisplatin cytotoxicity in cells; IRAK1/4 inhibitor impedes proliferation, migration in cells, and is effective in a xenograft model of HCC. |
| HCC [153] | HCC pt macrophages; STK-/- DEN mouse | IRAK1/4 inhibitor I | Tumor suppressor STK4 levels inversely correlate with IRAK1 in HCC macrophages; IRAK1/4 inhibitor I had anti-tumor effects in STK KO HCC mice. |
| HNSCC [43] | UMSCC1, UMSCC6, UMSCC47 cell lines | IRAK1/4 inhibitor I; IRAK1 shRNA | IRAK1 overexpressed in 14% of HNSCC; IRAK1 inhibition via shRNA or IRAK1/4 inhibitor I induced apoptosis in HNSCC cell lines. |
| NSCLC [157] | Pt FFPE tumor samples | NA | Significantly higher cytoplasmic, lower nuclear IRAK1 expression in tumor cells than normal epithelium; overexpressed early in sequential preneoplastic evolution. |
| Melanoma [158] | Malme-3M, SK-MEL-2, WM115, C32, RPMI-7951, A375, G361 cell lines; A375 xenograft mouse | IRAK1/4 inhibitor I | p-IRAK1 constitutively expressed in 42% of cell lines; IRAK1/4 inhibition enhances vinblastine, 5-FU cell killing; combining IRAK1/4 inhibitor I with vinblastine improved TGI and survival in a xenograft mouse model. |
| Melanoma [159] | M4Beu, 7GP122, T1P26R, FM516-SV, WM239, C8161, MeWo cell lines; newborn immunosuppressed rat | NA | IRAK1 gene expression elevated in highly metastatic versus normal variants of melanoma cells grafted into immunosuppressed newborn rats. |
BC, breast cancer; DEN, diethylnitrosamine; FFPE, formalin-fixed and paraffin-embedded; HCC, hepatocellular carcinoma; NA, not applicable; NSCLC, non-small cell lung cancer; OS, overall survival; TGI, tumor growth inhibition.