| First Author | Ma X | Year | 2017 |
| Journal | Oncogene | Volume | 36 |
| Issue | 28 | Pages | 4060-4071 |
| PubMed ID | 28319059 | Mgi Jnum | J:243363 |
| Mgi Id | MGI:5908303 | Doi | 10.1038/onc.2017.16 |
| Citation | Ma X, et al. (2017) CAMK2gamma in intestinal epithelial cells modulates colitis-associated colorectal carcinogenesis via enhancing STAT3 activation. Oncogene 36(28):4060-4071 |
| abstractText | Inflammation is one of the major risk factors for cancer. Here, we show that calcium/calmodulin-dependent protein kinase II gamma (CAMK2gamma) in intestinal epithelial cells (IECs) modulates inflammatory signals and promotes colitis-associated cancer (CAC) in mice. We have identified CAMK2gamma as a downstream target of colitis-induced WNT5A signaling. Furthermore, we have shown that CAMK2gamma protects against intestine tissue injury by increasing IEC survival and proliferation. Calcium/calmodulin-dependent protein kinase II gamma knockout mice displayed reduced CAC. Furthermore, we used bone marrow transplantation to reveal that CAMK2gamma in IECs, but not immune cells, was crucial for its effect on CAC. Consistently, transgenic over-expression of CAMK2gamma in IECs accelerated CAC development. Mechanistically, CAMK2gamma in IECs enhanced epithelial signal transducer and activator of transcription 3 (STAT3) activation to promote survival and proliferation of colonic epithelial cells during CAC development. These results thus identify a new molecular mechanism mediated by CAMK2gamma in IECs during CAC development, thereby providing a potential new therapeutic target for CAC. |
