Table 2.
An overview of established roles of GRK isoforms in various types of cancer.
| GRK Subtype | Type of Cancer | Interacting Partner (s) | Molecular Mechanism | Function | Biological Model | References |
|---|---|---|---|---|---|---|
| GRK2 | Thyroid carcinoma | TSHR | ND | Decrease proliferation through rapid desensitization | Differentiated thyroid carcinoma patients and cell lines | [120] |
| Hepatocellular carcinoma cell | IGFI-R | Decrease proliferation and migration | [121] | |||
| Human hepatocellular carcinoma (HepG2) | IGFI-R | Decrease cell cycle progression | [122] | |||
| Pancreatic cancer | N/A | ND | --T-stage and poor survival rate, increased proliferation | Pancreatic carcinoma patients, ductal adenocarcinoma patients and cell lines | [123] | |
| Breast carcinosarcoma | NGFR | Decrease bone cancer pain | [124] | |||
| Kaposi’s sarcoma-associated herpesvirus infected tumor cell | CXCR2 | Desensitization and AKT signaling | Decrease migration and invasion | Patients and cell lines | [125] | |
| Basal breast cancer with Her-2 amplification/infiltrating ductal carcinoma | Her-2/ER-α | Increase the promoting of mitogenic, anti-apoptic activities- survival and progression | [126] | |||
| Luminal and basal breast cancer | HDAC6/Pin1 | AKT/ERK cascades | Increase sensitivity of breast cancer cells to traditional chemotherapeutic treatment | Invasive ductal carcinoma patients, cell lines orthotopic and xenograftmouse models | [127] | |
| Breast cancer | CXCR4 | Desensitization and signaling | Decrease metastasis | Breast cancer patients, cell lines orthotopic mouse models | [128] | |
| Human gastric carcinoma cell line (MKN-45) | H2 receptor | --poor differentiation | [129] | |||
| Human breast cancer | N/A | Increase tumor growth and decrease angiogenesis | [130,131] | |||
| Prostrate | ND | Differentiation | Adenocarcinoma patients | [132] | ||
| Prostrate | ND | ND | ND | Neuroendocrine prostrate and metastatic castrastion-resistant prostate cancer patients | [133] | |
| Glioblastoma | ND | ND | Mesenchymal glioblastoma patients. | [134] | ||
| GRK2/4 | Ovary | ND | ND | Granulosa cell cancer patients | [135] | |
| GRK2/5/6 | Gastric cancer (SSTW-2) | recoverin | --tumor progression, metastasis | [136] | ||
| GRK2/6 | melanoma | Melanocortin 1 receptor | --determinant for skin cancer | [137] | ||
| GRK3 | Breast cancers (MDA-MB-231, MDA-MB-468 | CXCR4 | Decrease metastasis increase migration | Breast cancer patients, cell lines orthotopic mouse models | [138] | |
| Prostate cancer (PC3) | N/A | Downmodulation of angiogenesis inhibitors | Increase metastasis, tumor progression, angiogenesis | Metastatic castration-resistant prostate cancer patients, cell lines and orthotopic mouse models | [139] | |
| Retinoblastoma (Y-79) | CRFI receptor | Increase stress adaptation | [140] | |||
| Oral squamous carcinoma | β2-adrenergic receptor | --tumor malignancy and invasion | [128] | |||
| Glioblastoma | CXCR4 desensitization and signaling | desensitization and signaling | Increased proliferation | Classical Glioblastoma patients | [134] | |
| GRK4 | Ovarian malignant granulosa cell tumor | FSHR | --benign and malignant transformation in tumor development | [135] | ||
| Breast cancer | Arrestin2 receptor | Mediated ERK & JNK signaling | Increase proliferation | Ductal carcinoma patients and cell lines | [141] | |
| GRK5 | glioblastoma | N/A | Proliferation rate and WHO grade | Glioblastoma multiform patients and cell lines | [142] | |
| Thyroid carcinoma | TSHR | TSHR desensitization and signaling | Decrease proliferation through slow desensitization, increase proliferation | Differentiated thyroid carcinoma patients | [120] | |
| Prostate cancer (PC3) | Cyclin D1 | G2/M progression | Decrease proliferation, cell cycle | Cell lines and xenograft mouse tumors | [143] | |
| Prostate cancer (PC3, DU145, LNCaP) | Moesin | Moesin phosphorylation | Decrease migration, invasion Increase cell adhesion |
Cell lines and xenograft mouse tumors | [69] | |
| Prostate cancer | N/A | Increase tumor growth, invasion, and metastasis | [144] | |||
| Osteosarcoma (U2OS, Saos-2) | P53 | Phosphorylation and degradation | Decrease cell apoptosis and radiosensitivity | Cell lines | [145] | |
| Colon | PGE2 | Desensitization and signaling | Increased proliferation | Cell lines | [146] | |
| Kaposi’s sarcoma | KSHV-GPCR | Desensitization and signaling | Increased proliferation | Cell lines | [147] | |
| GRK6 | Heptocellular carcinoma | N/A | --proliferation maker in early diagnosis | [148] | ||
| Hypopharyngeal squamous cell carcinoma (FaDu) |
Methyl transferase | Methylation of GRK6 | --cancer progression Decrease invasion |
[149] | ||
| Medulloblastoma | CXCR4/ EGFR/ PDGFR-Src | Increase migration | [143] | |||
| Lung cancer | CXCR2 | Decrease cancer development | [150] | |||
| Lung | ND | ND | Decreased survival | Adenocarcinoma patients | [151] | |
| Medullo-Blastoma | CXCR4 | Desensitization and signaling | Increased migration | Medulloblastoma patients and cell lines | [143] | |
| Myeloma | STAT3 | phosphorylation | Increased survival | Primary multiple myeloma patients and cell lines | [94] | |
| GRK1/7 | recoverin | --cancer-associated retinopathy | [152] |
N/A: not provided by the research, --: has association with.