Table 2.
The calcium/calmodulin-stimulated protein kinase family mediate a variety of cancer-related functions in multiple cancer types in vitro. AML acute myeloid leukaemia; AIP autocamtide-2 inhibitory peptide; HCC hepatocellular carcinoma; siRNA small interfering RNA; shRNA short hairpin RNA; WT wild-type.
| Target | Cancer | Cell Line(s) | Method of Manipulation | Effect | Reference |
|---|---|---|---|---|---|
| CaMKK | Prostate | LNCaP | Pharmacological inhibition (STO-609) | Decreased proliferation | [89] |
| LNCaP, VCqP, C4-2B, 22Rv1 | siRNA and pharmacological inhibition (STO-609) | Decreased proliferation | [91] | ||
| LNCaP | siRNA and pharmacological inhibition (STO-609) | Decreased migration and invasion | [92] | ||
| LNCaP | CaMKKβ overexpression | Increased migration | [92] | ||
| LNCaP | CaMKKβ overexpression | Decreased proliferation | [90] | ||
| DU145 | CaMKKβ siRNA | Decreased proliferation | [107] | ||
| Gastric | AGS, KATO-III, SNU-16, N87 | CaMKKβ siRNA | Decreased proliferation | [85] | |
| SNU-1, N87 | CaMKKβ siRNA and pharmacological inhibition (STO-609) | Decreased proliferation and induced apoptosis | [108] | ||
| HCC | PHM1, SK-Hep1, HepG2 | CaMKKβ siRNA and pharmacological inhibition (STO-609) | Decreased proliferation | [86] | |
| Glioma | U-87MG | CaMKKβ siRNA | Decreased proliferation, migration and invasion | [87] | |
| Ovarian | SKOV-3, OVCAR-3 | CaMKKβ siRNA and pharmacological inhibition (STO-609) | Decreased proliferation and induced apoptosis | [88] | |
| Breast cancer | MCF-7 | CaMKKα and CaMKKβ siRNA | Arrested cells in G1 | [110] | |
| Medulloblastoma | DOAY | Expression of dominant negative CaMKK mutant | Decreased migration | [109] | |
| CaMKI | AML | MV-4-11, Kasumi-1 | shRNA and CaMKI overexpression | Downregulation decreased proliferation; Overexpression of kinase dead mutant decreased colony formation | [93] |
| Breast cancer | MCF-7 | siRNA | Arrested cells in G1 | [110] | |
| Medulloblastoma | DOAY | Expression of dominant negative CaMKI mutant | Decreased migration | [109] | |
| CaMKII | Osteosarcoma | MG-63, 143B, HOS | CaMKIIα shRNA and overexpression | Knockdown decreased proliferation, migration and invasion. Overexpression increased proliferation, migration, invasion | [101] |
| MG-63, 154B | Wild-type and K42M kinase dead CaMKIIα overexpression | K42M kinase dead overexpression reduced growth | [102] | ||
| AML | KG1, KCL22, THP-1, Kasumi-1 | Overexpression of kinase dead truncated CaMKIIγ, CaMKIIγ shRNA, pharmacological inhibition (KN-62, KN-93, KN-92) | Kinase dead overexpression, shRNA and pharmacological inhibition decreased colony formation and proliferation. | [98] | |
| Lung cancer | SCC-9, NCI-H345, NCI-H128, NCI-H146, NCI-H69 | Pharmacological inhibition (KN-62) | Slowed progression through S phase and decreased proliferation | [111] | |
| Medullary thyroid cancer | TT, MZ-CRC1 | Pharmacological inhibition (antCaNtide) | Decreased cell proliferation | [112] | |
| Colon cancer | HCT116 | Pharmacological inhibition (KN-92, KN-93) | Decreased proliferation, migration and invasion | [99] | |
| Gastric cancer | BGC-823 | Pharmacological inhibition (KN-93) and CaMKIIβ shRNA | Decreased cell proliferation and migration, induced apoptosis | [113] | |
| BGC-823 | Pharmacological inhibition (KN-62) and H282R constitutively active CaMKIIα overexpression | Pharmacological inhibition decreased cell proliferation. Overexpression of constitutively active increased cell proliferation, migration and invasion | [105] | ||
| Prostate cancer | C4-2B, LNCaP, PC3, DU145 | Pharmacological inhibition (KN-93) | Decreased proliferation | [114] | |
| 1542-CP3TX | Pharmacological inhibition (AIP) | Decreased cell migration | [115] | ||
| T cell lymphoma | H9 | CaMKIIγ knockout by CRISPR/Cas | Decreased proliferation and colony formation | [116] | |
| Breast cancer | MDA-MB-231, MCF-7 | Overexpression of CaMKIIα, T286D (phosphomimic) and T286V (phosphonull), Pharmacological inhibition (KN-92, KN-93, AIP) | Overexpression of WT and phosphomimic forms increased cell proliferation, migration and invasion. Pharmacological inhibition decreased migration and invasion | [100] | |
| MDA-MB-231 | Overexpression of CaMKIIα, T286D (phosphomimic) and T253D (phosphomimic) | Overexpression of WT and T286D increased proliferation. Overexpression of T253D decreased proliferation | [117] | ||
| Glioma | C6, U-251MG | Pharmacological inhibition (KN-93) | Decreased migration | [118] | |
| D54, H8a | Pharmacological inhibition (AIP) | Decreased migration | [119] | ||
| U-87MG | CaMKIIγ siRNA, pharmacological inhibition (KN-93) | Decreased proliferation, invasion and neurosphere formation | [120] | ||
| CaMKIV | AML | Lin− AML, MV-4-11, Kasumi-1 | CaMKIV and K75M overexpression and CaMKIV shRNA | CaMKIV-K75M overexpression and shRNA knockdown decreased colony formation. shRNA knockdown induced apoptosis and decreased proliferation. | [93] |
| U937 | CaMKIV wild-type and K71M kinase dead mutant overexpression | Cells arrested in G0/G1 following WT, but not K71M, overexpression | [121] | ||
| HCC | PHM1, SK-Hep1 | CaMKIV siRNA | Inhibited colony formation and proliferation | [86] |