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- Title
Wnt signaling controls radiosensitivity via cyclooxygenase-2-mediated Ku expression in head and neck cancer.
- Authors
Chang, Hyo Won; Roh, Jong-Lyel; Jeong, Eun-Jeong; Lee, Sang-wook; Kim, Seung-Whan; Choi, Seung-Ho; Park, Sung-Kyung; Kim, Sang Yoon
- Abstract
It has been proposed that Wnt signaling pathway may be a key radioprotective mechanism in irradiated cancer cells; however, the specific radioresistance mechanisms remain not to be fully clarified. Here we elucidate a novel signaling pathway of radioresistance in head and neck cancer (HNC) cell lines involving interactions among the Wnt signaling pathway, cyclooxygenase-2 (COX-2) and Ku expression. Activation of the Wnt signaling pathway by (2′Z,3′E)-6-bromoindirubin-3′-oxime (BIO) resulted in β-catenin cytoplasmic accumulation and translocation to the nucleus, upregulated Ku expression and increased radioresistance in the COX-2-expressing HNC cell line. In contrast, Wnt singaling activation by BIO had no effects on Ku expression and radiosensitivity in a HNC cell line negative for COX-2. Interactions between Wnt singaling and Ku were indirectly regulated by COX-2. Blockage of COX-2 signaling led to the suppression of β-catenin-induced Ku expression, and to consequent recovery of the radiosensitivity in HNC cells. Our results conclusively suggest that β-catenin plays a pivotal role in the regulation of Ku expression via the proposed COX-2 intracellular pathway, thus supporting a novel radioresistance mechanism of HNC. © 2007 Wiley-Liss, Inc.
- Publication
International Journal of Cancer, 2008, Vol 122, Issue 1, p100
- ISSN
0020-7136
- Publication type
Article
- DOI
10.1002/ijc.23069