Possible role of nuclear β-catenin in resistance to preoperative chemoradiotherapy in locally advanced rectal cancer.

Autor: Takahashi, Hiroyuki, Nakamura, Kie, Usami, Akane, Tsuruta, Tomoko, Hashimura, Miki, Matsumoto, Toshihide, Saegusa, Makoto
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Zdroj: Histopathology; Aug2017, Vol. 71 Issue 2, p227-237, 11p
Abstrakt: Aims β-Catenin signalling participates in the regulation of epithelial-mesenchymal transition ( EMT)/cancer stem cell ( CSC) properties. The aim of this study was to investigate the role of β-catenin in resistance to neoadjuvant chemoradiotherapy in patients with rectal cancer, especially pertaining to its association with EMT/ CSC features. Methods and results A total of 109 cases of locally advanced rectal cancer, along with a colon cancer cell line, were investigated. Nuclear β-catenin accumulation in pretreatment-biopsied samples was inversely associated with the therapeutic efficacy of chemoradiotherapy in resected rectal cancer. In resected tumours, nuclear β-catenin was predominantly observed in EMT-like lesions with decreased E-cadherin and increased Snail expression, along with expression of CSC-related markers. The EMT-like lesions also showed significant decreases in both apoptosis and cell proliferation as compared with non- EMT lesions. In-vitro culture of a colon cancer cell line in STK2 was sufficient to induce EMT/ CSC properties together with nuclear β-catenin accumulation, and showed inhibition of cell proliferation and resistance to doxorubicin treatment. Conclusion Nuclear β-catenin accumulation may contribute to chemoradioresistance in locally advanced rectal cancer, probably through its regulation of EMT/ CSC properties. In addition, nuclear β-catenin in pretreatment-biopsied samples is useful in predicting the efficacy of chemoradiotherapy in patients with rectal cancer. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index
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