1. CAMK2γ in intestinal epithelial cells modulates colitis-associated colorectal carcinogenesis via enhancing STAT3 activation
- Author
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Xiaoqiong Wang, Zhenzhou Xiao, Walter Tsark, Rongzhen Xu, Lihua Jin, Ying Gu, Min He, Byung-Wook Kim, Xiaoxian Gan, Jiawei Zhang, Hua Yu, Zhipeng Meng, John E. Shively, Xiaoxiao Ma, Wendong Huang, and Lili Ding
- Subjects
Colitis-associated colorectal cancer ,STAT3 Transcription Factor ,0301 basic medicine ,Cancer Research ,Carcinogenesis ,Inflammation ,Biology ,medicine.disease_cause ,digestive system ,Article ,STAT3 ,Mice ,03 medical and health sciences ,HT29 Cells ,0302 clinical medicine ,Growth factor receptor ,Intestinal mucosa ,Genetics ,medicine ,Animals ,Humans ,cardiovascular diseases ,Intestinal Mucosa ,Molecular Biology ,Cell Proliferation ,Mice, Knockout ,CAMK2γ ,nutritional and metabolic diseases ,Epithelial Cells ,Colitis ,HCT116 Cells ,3. Good health ,Mice, Inbred C57BL ,WNT5A ,030104 developmental biology ,inflammation ,030220 oncology & carcinogenesis ,Immunology ,Cancer research ,STAT protein ,biology.protein ,medicine.symptom ,Calcium-Calmodulin-Dependent Protein Kinase Type 2 ,Colorectal Neoplasms - Abstract
Inflammation is one of the major risk factors for cancer. Here, we show that calcium/calmodulin-dependent protein kinase II gamma (CAMK2γ) in intestinal epithelial cells (IECs) modulates inflammatory signals and promotes colitis-associated cancer (CAC) in mice. We have identified CAMK2γ as a downstream target of colitis-induced WNT5A signaling. Furthermore, we have shown that CAMK2γ 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 CAMK2γ in IECs, but not immune cells, was crucial for its effect on CAC. Consistently, transgenic over-expression of CAMK2γ in IECs accelerated CAC development. Mechanistically, CAMK2γ 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 CAMK2γ in IECs during CAC development, thereby providing a potential new therapeutic target for CAC.
- Published
- 2017
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