セッション情報 The 2nd JSGE International Topic Conference Poster Session

Caricinogenesis of Colon Cancer

タイトル IT-P-16:

Stabilization of Atoh1 Protein by TNF-α in Colon Cancer Acquires Cancer Stemness

演者 Fukushima Keita(Department of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University, Japan)
共同演者 Tsuchiya Kiichiro(Department of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University, Japan), Kano Yoshihito(Department of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University, Japan), Hibiya Shuji(Department of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University, Japan), Horita Nobukatsu(Department of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University, Japan), Zheng Xiu(Department of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University, Japan), Okamoto Ryuichi(Department of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University, Japan), Nakamura Tetsuya(Department of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University, Japan), Mamoru Watanabe(Department of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University, Japan)
抄録 The patients with ulcerative colitis are at increased risk of developing colitic cancer. Colitic cancer has been reported to acquire the chemoresistance, resulting in the poorer prognosis than that of sporadic colon cancer. However, how colitic cancer have malignant potential remains unknown. We therefore focus the pathological characteristic of colitic cancer that shows the enrichment of mucinous carcinoma and signet-ring cell carcinoma. We have previously reported that non-mucinous form of sporadic colon cancer is maintained by the proteasomal degradation of Atoh1 protein by which the differentiation toward goblet cells is regulated. However, interestingly, Atoh1 protein has been reported to stably express in mucinous carcinoma. We therefore hypothesized that inflammation might stabilize Atoh1 protein, resulting in the acquisition of mucinous form in colon cancer. Expectedly, treatment with TNF-α induced the expression of Atoh1 in sporadic carcinoma, resulting in the transformation to the mucinous form. For further analysis about the role of Atoh1 in colon cancer, we constructed Atoh1 mutant that are stably expressed in sporadic colon cancer. Stable expression of Atoh1 showed not only mucinous form but also cancer stemness such as Lgr5 and ALDH1 expression, tumorigenesis, cell migration, cell cycle arrest and chemoresistance. In conclusion, Atoh1 protein stabilized by TNF-α might acquire more malignant potential in colitic cancer.
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