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

被引：17
|
作者：
Takahashi, Hiroyuki [1 ]
Nakamura, Kie [1 ]
Usami, Akane [1 ]
Tsuruta, Tomoko [1 ]
Hashimura, Miki [1 ]
Matsumoto, Toshihide [1 ]
Saegusa, Makoto [1 ]
机构：
[1] Kitasato Univ, Sch Med, Dept Pathol, Sagamihara, Kanagawa, Japan
来源：
HISTOPATHOLOGY | 2017年 / 71卷 / 02期
关键词：
cancer stem cell; chemoradiotherapy; epithelial-mesenchymal transition; rectal cancer; -catenin; EPITHELIAL-MESENCHYMAL TRANSITION; CELL-LIKE PROPERTIES; STEM-CELLS; COLORECTAL-CANCER; METASTASIS; CARCINOMA; CHEMORESISTANCE; CHEMOTHERAPY; EXPRESSION; APOPTOSIS;
D O I：
10.1111/his.13227
中图分类号：
Q2 [细胞生物学];
学科分类号：
071009 ; 090102 ;
摘要：
Aims-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 -catenin in resistance to neoadjuvant chemoradiotherapy in patients with rectal cancer, especially pertaining to its association with EMT/CSC features. Methods and resultsA total of 109 cases of locally advanced rectal cancer, along with a colon cancer cell line, were investigated. Nuclear -catenin accumulation in pretreatment-biopsied samples was inversely associated with the therapeutic efficacy of chemoradiotherapy in resected rectal cancer. In resected tumours, nuclear -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 -catenin accumulation, and showed inhibition of cell proliferation and resistance to doxorubicin treatment. ConclusionNuclear -catenin accumulation may contribute to chemoradioresistance in locally advanced rectal cancer, probably through its regulation of EMT/CSC properties. In addition, nuclear -catenin in pretreatment-biopsied samples is useful in predicting the efficacy of chemoradiotherapy in patients with rectal cancer.
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收藏
页码：227 / 237
页数：11
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