Abstract Background: The Ataxia telangiectasia mutated (ATM) is a serine/threonine protein kinase that is recruited and activated by DNA double-strand breaks. Recently, ATM was reported to correlate with breast cancer metastasis by regulating phosphorylated Snail which was known as a marker of epithelial-mesenchymal transition (EMT), however, it remains unclear in colorectal cancer (CRC). In this study we attempted to clarify the impact of ATM on the mechanism of EMT in CRC. Methods: Potential ATM levels were evaluated in human CRC cells (HT29 and SW480) by qPCR and western blot analysis. Cells were induced EMT by treated with TGF-b, were confirmed by the change of EMT markers (i.e. N-cadherin, E-cadherin, Snail and twist). Next, ATM levels were down-regulated by siRNA and the impact on EMT were evaluated by EMT markers. Invasive potential was evaluated by scratch assay. Results: HT29 showed significantly higher levels of ATM comparing to SW480 (p = 0.042). N-cadherin (p = 0.065), Snail (p = 0.034) and twist (p = 0.052) were highly observed in HT-29, while similar level of E-cadherin in SW480 (p = 0.692). Scratch assay revealed that approximately 4 times high migration was observed in HT29. TGF-b induced EMT such as elevation of N-cadherin and Snail (E-cadherin was not affected), leading to promotion of cell migration in SW480. ATM was successfully 48.4% down-regulated (p = 0.001) in SW480, which resulted in reducing cell migration (p = 0.033). Conclusions: ATM might be a critical regulator of EMT in colorectal cancer invasion. Citation Format: Hidena Takahashi, Masashi Tsuruta, Hirotoshi Hasegawa, Koji Okabayashi, Ryo Seishima, Shimpei Matsui, Toru Yamada, Takayuki Kondo, Takehiro Shimada, Mutsuhito Matsuda, Masashi Yahagi, Yusuke Yoshikawa, Yusuke Asada, Kiyoaki Sugiura, Yoshiyuki Suzuki, Yuki Tajima, Junpei Nakadai, Yuko Kitagawa. Ataxia telangiectasia mutated relates to epithelial-mesenchymal transition in colorectal cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5193. doi:10.1158/1538-7445.AM2015-5193