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Possible role of nuclear β‐catenin in resistance to preoperative chemoradiotherapy in locally advanced rectal cancer
Author(s) -
Takahashi Hiroyuki,
Nakamura Kie,
Usami Akane,
Tsuruta Tomoko,
Hashimura Miki,
Matsumoto Toshihide,
Saegusa Makoto
Publication year - 2017
Publication title -
histopathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.626
H-Index - 124
eISSN - 1365-2559
pISSN - 0309-0167
DOI - 10.1111/his.13227
Subject(s) - colorectal cancer , catenin , medicine , cancer research , epithelial–mesenchymal transition , cancer stem cell , chemoradiotherapy , cancer , oncology , wnt signaling pathway , pathology , biology , metastasis , signal transduction , biochemistry
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 STK 2 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.