Journal
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Volume 438, Issue 1, Pages 97-102Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2013.07.032
Keywords
Kinesin-8 Kif18a; Tumorigenesis; Colitis-associated cancer; Knock-out mice; AOM-DSS model; Akt
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Funding
- Ministry of Science and Technology of China [2006BAI23B02, 2011BAI15B02]
- National Natural Science Foundation of China [81201365, 31000408]
- Science and Technology Commission of Shanghai Municipality [10JC1410300, 11DZ2292400, 12ZR1421100, 13140901400, 13DZ2280600]
- E-Institutes of Shanghai Municipal Education Commission [E03003]
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Kinesins are a superfamily of molecular motors involved in cell division or intracellular transport. They are becoming important targets for chemotherapeutic intervention of cancer due to their crucial role in mitosis. Here, we demonstrate that the kinesin-8 Kif18a is overexpressed in murine CAC and is a crucial promoter during early CAC carcinogenesis. Kif18a-deficient mice are evidently protected from AOM-DSS-induced colon carcinogenesis. Kif18A is responsible for proliferation of colonic tumor cells, while Kif18a ablation in mice promotes cell apoptosis. Mechanistically, Kif18a is responsible for induction of Akt phosphorylation, which is known to be associated with cell survival regulation. In conclusion, Kif18a is critical for colorectal carcinogenesis in the setting of inflammation by mechanisms of increased PI3K-AKT signaling. Inhibition of Kif18A activity may be useful in the prevention or chemotherapeutic intervention of CAC. (C) 2013 Elsevier Inc. All rights reserved.
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